Appetite 80 (2014) 41–54

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Appetite
j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / a p p e t

Research review

Cognitive and behavioural effects of sugar consumption in rodents.

A review ☆
Michael D. Kendig *
School of Psychology (A18), University of Sydney, Sydney, NSW 2006, Australia

A R T I C L E I N F O A B S T R A C T

Article history: The pronounced global rise in sugar consumption in recent years has been driven largely by increased
Received 2 December 2013 consumption of sugar-sweetened beverages. Although high sugar intakes are recognised to increase the
Received in revised form 13 April 2014 risk of obesity and related metabolic disturbances, less is known about how sugar might also impair cog-
Accepted 30 April 2014
nition and learned behaviour. This review considers the effects of sugar in rodents on measures of learn-
Available online 6 May 2014
ing and memory, reward processing, anxiety and mood. The parallels between sugar consumption and
addictive behaviours are also discussed. The available evidence clearly indicates that sugar consump-
Keywords:
tion can induce cognitive dysfunction. Deficits have been found most consistently on tasks measuring
Sugar
Learning spatial learning and memory. Younger animals appear to be particularly sensitive to the effects of sugar
Memory on reward processing, yet results vary according to what reward-related behaviour is assessed. Sugar does
Cognition not appear to produce long-term effects on anxiety or mood. Importantly, cognitive impairments have
Reward been found when intake approximates levels of sugar consumption in people and without changes to
weight gain. There remain several caveats when extrapolating from animal models to putative effects of
sugar on cognitive function in people. These issues are discussed in conjunction with potential under-
lying neural mechanisms and directions for future research.
© 2014 Elsevier Ltd. All rights reserved.

Introduction
A significant change to human diet composition in recent cen-
turies has been the increase in intake of sugars, with an estimated
rise in per capita consumption from 5 kg to 70 kg per year from 1800
to 2006 (Tappy, 2012). Rising sugar consumption is no longer unique
to North America and now affects the majority of the developed and
developing world (Basu, McKee, Galea, & Stuckler, 2013; Lustig,
Schmidt, & Brindis, 2012). This increase is largely attributable to rising
consumption of sugar-sweetened beverages (SSBs), which contrib-
uted to 80% of the increase in added sugar consumption during the
period 1962–2000 in the USA (Popkin & Nielsen, 2003) and which
today are easily the largest single source of added sugar consump-
tion (Yang et al., 2014). The percent contribution of SSBs to total
caloric intake has also increased for both adults (Duffey & Popkin,
2007) and children and adolescents (Wang, Bleich, & Gortmaker,
2008). Today most individuals draw between 5% and 20% of total
calories from added sugar, although this proportion is over 25% for
☆
Acknowledgements: The author is supported by an Australian Postgraduate Award
scholarship and is grateful to Laura Corbit and Robert Boakes for insightful com-
ments on drafts of the manuscript. An earlier draft of this manuscript formed the
introduction to the author’s Master of Science research thesis.
* E-mail address: mken5980@uni.sydney.edu.au.
13% of the American population (Marriott, Olsho, Hadden, & Connor,
2010) and above 20% for many adolescents (Krebs-Smith, 2001).
Consuming too much sugar is increasingly viewed as a risk factor
for many chronic diseases and not simply obesity and dental caries
(Schmidt, 2014). Meta-analyses have found higher levels of sugar
intake to be associated not only with weight gain (Te Morenga,
Mallard, & Mann, 2013) but also with metabolic syndrome and type-2
diabetes (Malik & Hu, 2012) and cardiovascular disease incidence
and mortality (Malik et al., 2010; Yang et al., 2014). Additionally, in-
tervention studies have reported SSB-induced metabolic damage in
the absence of total body weight change or total energy intake
(Aeberli et al., 2011; Maersk et al., 2012). In light of this research,
calls for public health interventions targeted at reducing the disease
burden associated with sugar (e.g. Brownell et al., 2009; Lustig et al.,
2012) have been followed by changes to public policy. A well-
documented example is the introduction of taxes on SSBs by several
governments in recent years, with a recent meta-analysis suggest-
ing that this approach is effective (Escobar, Veerman, Tollman,
Bertram, & Hofman, 2013). Additionally, the World Health Organ-
ization’s current draft guidelines on sugar now advise that sugar
comprise <5% of total energy intake, beyond the stated upper limit
of 10% introduced in the 2003 guidelines (World Health Organization,
2014). Lastly, some epidemiological studies (Bray, Nielsen & Popkin,
2004) and studies in animals (e.g. Thresher, Podolin, Wei, Mazzeo,
& Pagliassotti, 2000) have suggested that the harmful metabolic
effects of sugar are primarily attributable to the monosaccharide fruc-

http://dx.doi.org/10.1016/j.appet.2014.04.028
0195-6663/© 2014 Elsevier Ltd. All rights reserved.
42 M.D. Kendig/Appetite 80 (2014) 41–54
tose, which, together with glucose, form one-half of sucrose.
However, others contend that the experimental conditions used to
elicit these effects are not representative of fructose consumption
in the human diet, and that the effects of fructose are often equiv-
ocal when consumed at more moderate levels (Tappy & Mittendorfer,
2012; White, 2013).
Animal models, which allow for stricter control over diet and ex-
traneous variables than studies in people, have found that rodents
given free access to highly concentrated sugar solutions (above 30%
w/vol) commonly show accelerated body weight gain and adipos-
ity amongst other metabolic impairments (Chen et al., 2011; Kanarek
& Orthen-Gambill, 1982; Kawasaki et al., 2005; Lindqvist, Baelemans,
& Erlanson-Albertsson, 2008; Sclafani, 1987), and can also develop
metabolic impairments without changes to body weight gain (Soares
et al., 2013). Rodents fed lower concentrations comparable with those
of SSBs, such as 10% sucrose solution, can also develop metabolic
damage, although weight gain is normally unchanged as animals
compensate for the calories in solution by reducing their consump-
tion of solid chow (e.g. Avena, Bocarsly, & Hoebel, 2012; Sheludiakova,
Rooney, & Boakes, 2012), with some exceptions (e.g. Chan, Kendig,
Boakes, & Rooney, 2013; Kendig, Rooney, Corbit & Boakes, 2014b).
Feeding sugar as part of a solid diet can induce metabolic distur-
bances, reduce reproductive success and lower lifespan in rodents
(Chicco et al., 2003; Hulman & Falkner, 1994; Preuss et al., 1991; Ruff
et al., 2013), but this method is less reliably associated with hyper-
phagia and obesity (Sclafani, 1987).
Sugar and behaviour
In contrast to extensive research on the physical health effects
of sugar consumption, less is known about how sugar affects
behaviour and cognition. A popular and persisting theory is that sugar
fosters hyperactive or aggressive behaviour, particularly in chil-
dren. This view was informed by early studies reporting positive as-
sociations between sugar consumption and levels of restless and
“destructive–aggressive” behaviours in children (e.g. Prinz, Roberts,
& Hantman, 1980), and that removing sugar from the diet im-
proved the behaviour of juvenile prison inmates (Schoenthaler, 1983)
and hyperactive children (Crook, 1974). A more recent cross-
sectional study of adolescents found that the odds ratios for mental
difficulties (encompassing measures of mental distress, hyperac-
tivity and conduct problems) were highest in those reporting the
greatest levels of SSB consumption (~800 ml or more/day; Lien, Lien,
Heyerdahl, Thoresen, & Bjertness, 2006). However, in a sample of
Korean fifth-grade children, Kim and Chang (2011) found no rela-
tionship between consumption of simple sugars and the develop-
ment of ADHD.
The relationship between sugar and hyperactivity/aggression seen
in some correlational studies contrasts the results of the bulk of ex-
perimental studies, which have found no effect of sucrose on
behaviour and cognition. A meta-analysis of 23 double-blind inter-
vention studies found no significant effects of sugar on 14 behavioural
measures (Wolraich, Wilson, & White, 1995). Null effects of sugar
ingestion have been reported in laboratory-based studies of “sugar-
responsive” children (e.g. Kruesi, Rapoport, Cummings, & Berg, 1987)
and in children diagnosed with ADHD as well as age-matched chil-
dren without ADHD (Wender & Solanto, 1991). Studies conducted
over the longer term and in the home environment report similar
results; for example, a home-based dietary intervention study where
“sugar-sensitive” children were fed sucrose-, aspartame- or saccharin-
sweetened diets for 3-week periods found no differences on 31 cog-
nitive and behavioural outcomes measured weekly (Wolraich et al.,
1994). A review by Benton (2008) concluded that there was no ev-
idence for any negative effects of sugar on behaviour, and re-
ported that three putative mechanisms by which sugar is thought
to cause behavioural problems – intolerance to sugar, reactive
hypoglycaemia following ingestion, and reduced intake of essen-
tial micronutrients – were not supported in literature.
Thus, there does not appear to be a causal relationship between
sugar consumption and hyperactive, aggressive or antisocial
behaviours. Although this is inconsistent with the positive corre-
lations found in some cross-sectional, population-based studies, it
has been suggested that the latter effects are explained by reverse
causation, such that children who are hyperactive or who have
behavioural difficulties are more inclined to consume greater levels
of sugar (Bellisle, 2004; Benton, 2008). As outlined in this review,
however, increasing evidence from animal models indicates that
other aspects of behaviour and cognition can be affected in animals
fed a diet supplemented with sugar.
Sugar, reward and addiction
As a highly palatable and calorie-dense food, sugar activates brain
regions involved in reward processing as well as energy regula-
tion (Kenny, 2011). Indeed, the activation of brain reward circuitry
by palatable foods is thought to override homeostatic signals and
stimulate unnecessary eating to promote obesity development
(Volkow & Wise, 2005). When lever-pressing for sucrose, rats show
enhanced c-fos protein activation in limbic brain regions involved
in reward as well as in hypothalamic areas involved in feeding
behaviour (Figlewicz, Bennett-Jay, Kittleson, Sipols, & Zavosh, 2011).
Furthermore, consumption of a sucrose solution triggers opioid and
dopamine release in the nucleus accumbens, with downstream
effects on other limbic and forebrain regions (Pomonis et al., 2000)
and dopamine and opioid antagonists can selectively block the re-
inforcing properties of sucrose (for review, see Levine, Kotz, & Gosnell,
2003). Additionally, the hedonic properties of sweet tastes may out-
compete those of drugs of abuse. A frequently cited example is the
finding that in a two-lever choice task, an overwhelming majority
of rats (94%) preferred to lever-press for sucrose and saccharin so-
lutions than for intravenous cocaine (Lenoir, Serre, Cantin, & Ahmed,
2007).
Much has been made of observations that similar neural circuit-
ry is activated by food and drug rewards. This has prompted con-
sideration of the parallels between obesity and drug addiction,
although this comparison has received criticism (see Ziauddeen,
Farooqi, & Fletcher, 2012). Arguably a more pertinent question is to
consider whether palatable foods themselves, such as sugar, can
come to elicit addiction-like behaviours. To this end, Hoebel and col-
leagues developed an animal model in which rats are maintained
on a cycle involving 12 h access to a sucrose or glucose solution and
chow (commencing 4 h into the dark cycle) followed by a 12 h period
of food and sugar deprivation. Consumption of the sugar solution
increases over days and is defined as “bingeing”, as rats with inter-
mittent access come to consume large amounts within the first hour
of access and consume as much sugar in 12-h as rats given ad-
libitum access do in 24-h (Avena, Rada, & Hoebel, 2008b). Animals
exposed to this intermittent access protocol demonstrate behavioural
and neurochemical withdrawal symptoms (e.g. elevated plus-
maze anxiety and teeth chattering; dopamine/acetylcholine imbal-
ance; Avena, Bocarsly, Rada, Kim, & Hoebel, 2008a; Colantuoni et al.,
2002); cross-sensitisation to amphetamine (Avena & Hoebel, 2003);
craving for sucrose (responding at a greater rate to obtain it) and
sensitisation of opioid and dopamine receptors in the striatum, hip-
pocampus, and other midbrain areas (Colantuoni et al., 2001).
While these findings are suggestive of an addiction-like profile
induced by sucrose consumption, an important point is that since
rats fed sucrose continuously do not show this phenotype, it appears
to be driven not by the consumption of sucrose per se, but rather
by the intermittent access conditions under which it is presented
(Corsica & Pelchat, 2010; Corwin & Grigson, 2009). Benton (2010)
considered data from the Avena/Hoebel model to evaluate evi-
 M.D. Kendig/Appetite 80 (2014) 41–54
dence for sugar addiction and its contribution to obesity and binge
eating disorders in people. The predictions derived from the animal
model examined in this review were not supported in human lit-
erature. There is thus ongoing debate about the existence of sugar
addiction on conceptual and empirical grounds. Whether or not this
profile can be conceptualised as an addiction to sugar, these pro-
nounced behavioural and neurochemical effects of intermittent sugar
consumption may nonetheless provide insights into aspects of
human eating behaviour.
Animal studies of sugar consumption on cognition and
behaviour
Research on sugar addiction necessarily involves studying
behaviours related to seeking, working for, or not having sugar. In
contrast, the effects of sugar on other reward-related behaviours are
less well understood. More broadly, little is known about how long-
term consumption of sugar affects learning and memory (as dis-
tinct from the documented short-term effects of glucose on memory,
cf. Messier, 2004) or other cognitive processes not related to ob-
taining or processing rewards. Thus, this review systematically
reviews the long-term behavioural and cognitive effects of sugar con-
sumption as examined in animal research. In most instances, the
animals used in the studies reviewed were laboratory rats (see
Table 1). There is evidence from research in people to suggest that
differences in diet composition affect cognitive function. For example,
Francis and Stevenson (2011) found that in undergraduate stu-
dents, higher self-reported intakes of saturated fat and refined sugars
were associated with poorer performance on hippocampal-
dependent memory tasks, poorer recollection of a recent meal and
insensitivity to satiety signals. However, it is difficult in people to
isolate the specific effects of sugar on cognition from those of other
dietary elements, and to rule out potentially confounding lifestyle
factors such as physical activity and socio-economic status. Animal
models can provide a greater level of control over these environ-
mental factors while systematically manipulating aspects of the diet.
Experiments were found through literature searches on PubMed,
Google Scholar, Web of Science, Ovid SP and the grey literature da-
tabase http://www.opendoar.org. Combinations of the keywords
“sucrose”, “sugar”, “glucose” or “fructose” were entered with
“behavio[/u]r”, “cognition”, “memory”, “learning” or “reward”. Only
experiments that systematically manipulated exposure to sugar and
that included a behavioural or cognitive outcome measure were in-
cluded. When sugar was administered as part of a high-fat, high-
sugar diet, (alternatively termed “junk-food”, “western” or “cafeteria”
diets), studies were included only if the design allowed specific effects
of sugar to be identified. The term “sugar” here refers to those that
contribute to the majority of added sugar consumption in people;
that is, the disaccharide sucrose; either of the monosaccharides
glucose or fructose; or any fructose/glucose mixture. Studies are
grouped according to the type of outcome measure assessed and
summarised results are presented in Table 1. While the sugar pro-
tocol is described explicitly for each experiment in the text below,
access to chow was ad-libitum unless stated otherwise.
Learning and memory
Morris water maze
A number of studies have examined the effects of sugar diets on
spatial learning and memory in the Morris Water Maze (MWM). In
this behavioural assay rats are placed into a large circular pool con-
taining a small platform submerged below the surface of the water
(made opaque with skim-milk or paint polymer), which the rats learn
to locate using large visual cues located around the perimeter of the
maze (Morris, 1984). The latency to locate the platform decreases
43
over repeated training sessions – i.e. performance improves – and
a slower or nonexistent decrease reflects impaired spatial learn-
ing. The most common form of test for spatial memory involves re-
moving the platform for a brief probe trial where the accuracy of
search behaviour is measured (e.g. number of entries into and time
spent in the area near the platform). Intact hippocampal function
is required for spatial learning and memory in the MWM, al-
though lesions to several other brain regions such as the cerebel-
lum and striatum have also been found to impair aspects of MWM
performance (D’Hooge & De Deyn, 2001).
Jurdak, Lichtenstein, and Kanarek (2008) found that after 5 weeks
free access to 32% sucrose solution, vegetable fat or chow only,
sucrose- but not fat-fed young male rats showed impaired spatial
learning and memory in the Morris Water Maze (MWM). Both
sucrose- and fat-fed rats gained more weight and deposited more
epididymal fat than controls, but only the sucrose group showed
elevated fasting blood glucose and higher serum triglyceride levels.
Soares et al. (2013) found that adult rats fed 35% sucrose solution
for 9 weeks showed impaired spatial memory in the MWM. These
deficits emerged in the absence of body weight change, but were
accompanied by insulin resistance and glucose intolerance. Defi-
cits in spatial learning and memory in the MWM have also been
shown after 25 weeks of consumption of 10% sucrose solution in
transgenic mice susceptible to Alzheimer’s disease (Cao, Lu, Lewis,
& Li, 2007). A study from our laboratory found that 28 days of 2-h
access to 10% sucrose solution in adolescent and young adult hooded
Wistar rats produced deficits in spatial memory (but not learning)
in the MWM that were still evident 7 weeks after rats last con-
sumed sucrose (Kendig, Boakes, Rooney, & Corbit, 2013). In con-
trast, in singly housed adult albino Wistar rats we recently found
that learning and memory in the MWM was unaffected by 9 weeks
of access to 10% sucrose or 10.4% maltodextrin solution for 2-h/
day or 24-h/day (Kendig, Lin, Beilharz, Rooney, & Boakes, 2014a).
Similarly, Jurdak (2009, unpublished thesis) found no differences in
MWM acquisition performance in rats fed 32% sucrose solution ad
libitum for 48 days in an experiment where the protein content of
the solid diet was also manipulated.
Land-based memory tasks
Sugar-induced memory deficits have also been reported in studies
using land-based spatial tasks. Agrawal and Gomez-Pinilla (2012)
tested whether the effects of 6 weeks of consumption of 15% fruc-
tose solution on spatial memory, peripheral and in-brain insulin re-
sistance in rats could be ameliorated by concurrent access to an n-3
fatty acid (docosahexaenoic acid; DHA). After the diet interven-
tion, rats fed fructose showed poorer long-term spatial memory on
the Barnes Maze by exhibiting longer latency times to escape the
maze. Fructose-fed rats also showed peripheral metabolic dysfunc-
tion (elevated serum glucose, insulin and triglycerides) and altered
in-brain insulin signalling and synaptic plasticity. Importantly, the
degree of memory impairment on the Barnes maze was positively
correlated with plasma triglyceride levels and insulin resistance,
which itself was negatively correlated with tyrosine phosphoryla-
tion in hippocampal insulin receptors. These relationships suggest
that insulin function may mediate sugar-induced cognitive impair-
ment. Interestingly, DHA supplementation buffered against the
fructose-induced deficits on cognitive, metabolic and neural
measures.
Soares et al. (2013) found that rats fed 35% sucrose solution for
9 weeks demonstrated poorer short-term memory on a modified
Y-maze task by making fewer entries into, and spending a lower pro-
portion of time in, a novel arm of the maze revealed at test. Anal-
ysis of the hippocampus indicated that relative to controls, sugar-
fed rats exhibited a decreased density of insulin and glucocorticoid
receptors, and alterations to some glutamatergic receptors; however,
 44
Table 1.
Summary of studies on cognitive and behavioural effects of high-sugar diets, grouped according to type of measure assessed.

Domain Authors Sugar protocol % calories as sugara Animals/age at Behavioural test/s and result Metabolic/neurobiological effects
sugar treatment

Learning and Agrawal and 15% fructose solution ad-libitum for 6 Details not Male adult Barnes maze: Impaired spatial memory ↑ insulin resistance, fasting insulin and
memory Gomez-Pinilla weeks, with or without n-3 fatty acid supplied Sprague-Dawley (latency to escape) in fructose-fed rats; triglycerides, disrupted hippocampal
(2012) in solid diet rats no differences during training insulin signalling in fructose rats
Beilharz et al. 10% sucrose solution ad-libitum for 45.1% for suc + Male adult Object and place recognition tests: No effect of suc alone on body weight
(2013) 21 days, with or without a high-fat/ chow rats; 2.3% Sprague-Dawley sucrose-fed rats, with or without high- gain, white adipose tissue, plasma
high-sugar solid diet (e.g. cakes, from suc solution rats energy solid diet, were impaired on leptin. ↑ hippocampal TNF-α/IL-1β in
biscuits) in HFHS+ suc rats place but not object recognition tasks suc-fed rats (trend)
after 5 days on diet.
Cao et al. (2007) 10% sucrose solution ad-libitum for 25 43% Male APP/PS1 mice Morris water maze: Impaired spatial ↑ body weight, fasting insulin and
weeks (transgenic model learning (latency to platform) and triglycerides, glucose intolerance in
of Alzheimer memory (# platform crossovers) in suc-fed mice
disease) suc-fed rats.
Chepulis et al. 7.9% sucrose, 10% honey or no sugar in 7.9% Male 8-week-old Y-maze: Suc-fed rats performed most ↑ body weight and fat content in suc-

M.D. Kendig/Appetite 80 (2014) 41–54

(2009) ad-libitum solid diet for 1 year Sprague-Dawley poorly (recognition of novel arm) fed rats
rats Object recognition: no suc effects
Hendley et al. Amstar sucrose pellets ad-libitum in 36–39% (chronic); Male/Female 7- to Electrified plus maze (correct ↑ plasma glucose and insulin in suc-fed
(1987) home cage for 15–18 days or overnight. 30–36% (overnight) 78-week-old avoidance of shocked arm in maze): no rats
Wistar–Kyoto rats effect of sucrose
Jurdak (2009; 32% sucrose solution ad-libitum in a 25.65%, 19.46% for Male 8-week-old Morris water maze: no differences in No effect of suc on body weight or
unpublished high- or low-protein diet for 10 weeks high-, low-protein Long Evans rats latency over 3 days acquisition. glucose tolerance
thesis) groups
Jurdak et al. (2008) 32% sucrose solution ad-libitum for 6 56.3% Male ~6-week-old Morris water maze: Impaired learning ↑ body weight, fasting glucose and
weeks Long-Evans rats (latency to platform) and memory triglycerides, epididymal fat, glucose
(time in target quadrant) in suc-fed intolerance in suc-fed rats
rats.
Jurdak and Kanarek 32% sucrose solution ad-libitum for 8 43.8% Male 6-week-old Novel object recognition: lower % ↑ body weight, fasting glucose and
(2009) weeks Long-Evans rats exploration of novel object in suc-fed epididymal fat, glucose intolerance in
rats suc-fed rats
Kendig et al. 10% sucrose or 10.4% maltodextrin For Exp. 1/2/3, Suc Male adult Wistar Morris water maze: no effect of ↑ body weight and retroperitoneal fat
(2014a) solutions 2-h/day for 11 weeks (Exp. 1), rats: 5.5/38.8/ rats sucrose or malto in Exp. 1 or Exp. 2. in suc- and malto-fed rats in Exps. 2
ad-libitum for 11 weeks (Exp. 2) or ad- 35.5%; Malto rats: Object and place recognition tests: and 3 but not Exp. 1. No differences in
libitum for 17–18 days (Exp. 3) 7.1/46.5/36.7% both sucrose- and maltodextrin-fed fasting glucose in Exp. 2
rats were impaired on place but not
object recognition tasks after 17 days
on diet.
Kendig et al. (2013) 10% sucrose solution, 2-h/day for 4 11.8% for Male 4- or 8-week- Morris water maze: impaired memory ↑ fasting blood glucose in suc-fed rats
weeks adolescents, 12.6% old kooded Wistar (distance from/time in target region) in
for adults rats suc-fed rats
Soares et al. (2013) 35% sucrose solution ad-libitum for 9 69.2% Male 4-month-old Modified Y-maze task: impaired ↑ fasting insulin and triglycerides,
weeks Wistar rats memory (less % time in novel arm) in altered hippocampal insulin function
suc-fed rats in suc-fed rats. Fasting BGL, body
Morris water maze: Impaired memory weight unaffected
(time in and latency to cross target
area) in suc-fed rats.
Table (continued)

Domain Authors Sugar protocol % calories as sugara Animals/age at Behavioural test/s and result Metabolic/neurobiological effects
sugar treatment

Instrumental Messier et al. 15% fructose solution ad-libitum for Intake not Male 3-month-old Operant bar-pressing task: improved No effect of fructose on body weight or
learning (2007) 3 months (with or without high-fat measured C57BL/6 mice learning in fructose-only group (more glucose tolerance
diet) lever-presses for pasta reward on days
4–5 of training using an FR-1 schedule
Kanoski et al. 22% sucrose or 22% glucose high-fat 220.5 g sucrose or Male 90-day-old Reversal learning: no group Only free access to glucose/high-fat
(2007) powdered diet ad-libitum or restricted glucose per kg Sprague-Dawley differences. Latent reversal task: no diet reduced BDNF in hippocampus
(85%) for 90 days solid diet rats differences between suc-fed and and frontal cortex
control rats; glucose-fed rats impaired
Kendig et al. 10% sucrose solution ad-libitum for 41.4% Male 3-month-old Reversal learning: no effect of sucrose ↑ retroperitoneal and epididymal fat
(2014b; 8 weeks Wistar rats after 6-week food restriction in suc-fed
Experiment 2) rats. Fasting BGL, body weight
unaffected
Reward Cottone et al. 50% sucrose in solid diet, 2 days/week 50% Male 6- to 7-week- Progressive ratio task: ↓ breakpoint for No effect of suc on weight gain
processing (2008) for 5 weeks old Wistar rats a less-preferred but palatable diet, ↓
Rft earned, ↑ latency to earn Rft in suc-
fed rats when suc diet unavailable

M.D. Kendig/Appetite 80 (2014) 41–54

Frazier et al. (2008) Sucrose pellets ad-libitum in home Details not Male/Female Progressive ratio task: ↓ breakpoint for No effect of suc exposure on fasting
cage for 4 or 7 weeks supplied C57BL/6 mice; suc pellets in suc-fed mice glucose or glucose tolerance. Suc-fed
sucrose access 3–7 Concurrent choice task: suc-fed mice mice gained more weight when
or 3–10 weeks of preferred to eat freely available chow exposed to a high-fat, high-sugar diet
age than press for suc pellets as adults
Sucrose preference: reduced in suc-fed
mice

Iemolo et al. (2012) 50% sucrose in solid diet, 2 days/week 50% Male 6- to 7-week- Intracranial self-stimulation threshold: No effect of suc on weight gain
for 7 weeks old Wistar rats no suc effects
Kendig et al. 10% sucrose solution ad-libitum for 36.3% for albino Male 4-month-old Outcome devaluation: no effect of ↑ BGL, insulin resistance,
(2014b; 8 weeks rats, 53.1% for albino and hooded sucrose on habit formation; suc-fed retroperitoneal fat in suc-fed rats. ↑
Experiment 1) hooded rats Wistar rats albino rats showed insensitivity to weight gain in suc-fed albinos only
motivational shift
Kendig et al. (2013) 10% sucrose solution, 2-h/day for 11.8% for Male 4- or 8-week- Outcome devaluation: adult suc-fed ↑ fasting blood glucose in suc-fed rats
28 days adolescents, 12.6% old hooded Wistar rats showed accelerated habit
for adults rats formation; adolescent suc-fed rats did
not show sensitivity to devaluation.
Martin and 10% sucrose intermittently 4 days/ 25.7%, 46.1% for 2-h Male Sprague- 12 h preference test (10% suc vs. ↓ stress-induced activation of lateral
Timofeeva (2010) week, 2- or 24-h/day, or ad-libitum, for and 24-h/day Dawley rats (200– water): sustained elevation in licks for septum in intermittent suc-fed rats.
6 weeks, with or without restraint intermittent 225 g) sucrose in rats with history of Suc access buffered against stress-
stress groups; 53.95% for intermittent suc access induced weight loss
ad-libitum rats
Pian et al. (2009) 10% sucrose solution with or without Details not Male adolescent Ethanol consumption: ↑ intake of suc- No effect of suc on weight gain
milk, 1-h/day, 5-day/week for 3 weeks supplied Wistar rats (suc in sweetened ethanol in suc-fed rats
PND29–51) Consumption and preference: ↑
consumption of sucrose, milk and
sucrose-milk in suc-fed rats
Sato et al. (1991) 10% sucrose solution ad-libitum for 3 36.5% Male adolescent Suc preference: ↑ preference for 30% ↑ weight gain in suc-fed rats. ↑
weeks rats (suc in PND- suc versus water in later life dopaminergic metabolism in
21–42) hypothalamus in suc-fed rats
(continued on next page)

45
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Table (continued)

Domain Authors Sugar protocol % calories as sugara Animals/age at Behavioural test/s and result Metabolic/neurobiological effects
sugar treatment

Vendruscolo et al. 5% sucrose solution ad-libitum (with or Details not Male adolescent Preference tests: ↓ saccharin No effect of suc on weight gain
(2010a) without 5% ethanol) for 16 days supplied Wistar rats (suc in consumption, ↓ ethanol preference in
PND30–46) suc-fed rats
Intravenous self-admin: lower
responding for saccharin in suc-fed
rats, no differences for ethanol
Vendruscolo et al. 5% sucrose solution ad-libitum (with or 20.6% Male adolescent Progressive ratio test: lower breakpoint No effect of suc on weight gain
(2010b) without 5% ethanol) for 16 days (suc in PND30–46) for saccharin and maltodextrin, not
or adult (suc in cocaine, in adolescent suc-fed rats
PND60–76) Wistar Concentration-response test: lower
rats response rates for saccharin, not
maltodextrin or cocaine, in adolescent
suc-fed rats
Wurtman and 0%, 12% or 48% sucrose in solid diet ad- 12% or 48% Male adolescent Diet during PND16-30 did not affect None reported
Wurtman (1979) libitum for 14 days Sprague-Dawley diet choice in PND30-63, when all
rats (suc in PND16– three diets were freely available
30)

M.D. Kendig/Appetite 80 (2014) 41–54

Anxiety Cao et al. (2007) 10% sucrose solution ad-libitum for 25 43% Male APP/PS1 mice Elevated plus maze, open field, T-maze ↑ body weight, fasting insulin and
weeks (transgenic model tests: no suc effects triglycerides, glucose intolerance in
of Alzheimer suc-fed mice
disease)
Chepulis et al. 7.9% sucrose, 10% honey or no sugar in 7.9% Male 8-week-old Elevated plus maze: no suc effects; ↑ body weight and fat content in suc-
(2009) ad-libitum solid diet for 1 year Sprague-Dawley reduced anxiety in honey-fed rats fed rats
rats
Hendley et al. Amstar sucrose pellets ad-libitum in 36–39% (chronic); Male/female 7- to Spontaneous activity: no suc effects ↑ plasma glucose and insulin in suc-fed
(1987) home cage for 15–18 days or overnight 30–36% (overnight) 78-week-old Habituation to novel cage: impaired in rats
Wistar–Kyoto rats female hyperactive strain given
overnight suc access
Distractibility: female hyperactive
strain fed chronic sucrose did not
habituate to context when internal
stimuli changed
Mood effects when Avena et al. 10% sucrose solution, 12-h/day for Details not Male Sprague- Elevated plus maze: ↑ anxiety in sugar- No effect of suc on body weight gain
sugar is (2008b) 28 days (coincides with chow access) supplied Dawley rats fed rats after 36-h fast
withdrawn Cottone et al. 50% sucrose in solid diet, 2 days/week 50% Female adolescent Elevated plus maze: ↑ anxiety in suc- ↑ body weight gain and adiposity,
(2009) for 8–9 weeks (6–7 weeks old) fed rats, restored when diet available some inflammatory markers ↑ in suc-
Wistar rats Defensive withdrawal test: ↑ hide time fed rats
in suc-fed rats, restored when diet
available
Iemolo et al. (2012) 50% sucrose in solid diet, 2 days/week 50% Male adolescent Forced swim test: ↑ immobility in suc- No effect of suc on body weight gain
for 7 weeks (6–7 weeks old) fed rats, restored when suc diet
Wistar rats available
Sucrose preference: ↓ in suc-fed rats,
restored when suc diet available
Maracle (2012; 10% sucrose solution, 12-h/day or ad- Details not Male Long-Evans Conditioned suppression: only No effect of suc on body weight gain
unpublished libitum for 28 days, supplied rats intermittent suc-fed rats did not
thesis) suppress lever-pressing during shock-
paired CS after 1 and 28 days
abstinence from suc.
a Where this information was not provided it was calculated, where possible, using information in the text and a caloric density of sucrose of 3.94 kcal/g unless otherwise stated.
 M.D. Kendig/Appetite 80 (2014) 41–54
no effects were found on measures of oxidative stress and inflam-
matory markers. A long-term study by Chepulis, Starkey, Waas, and
Molan (2009) maintained rats on solid diets containing 7.9% sucrose,
10% honey or no sugar for 1 year, and measured spatial memory in
a Y-maze task at 3-month intervals. Analysis suggested that per-
formance over the repeated tests was best in the honey-fed rats,
poorest in sugar-fed rats, and intermediate in the sugar-free control
groups. Another experiment measured spatial memory in rats in a
plus maze using a shock-avoidance paradigm, and found that prior
access to sucrose pellets in the home cage for 15–18 days (in addi-
tion to chow) had no effect on performance (Hendley, Conti, Wessel,
Horton, & Musty, 1987).
The effects of sugar on memory have also been studied using the
novel object location and novel object recognition tests, which
measure spatial and non-spatial short-term memory, respectively.
These tests rely on rats’ innate preference to explore objects that
are unfamiliar or in a new location, and do not require food depri-
vation or other prior learning (Dix & Aggleton, 1999). In the stan-
dard version of this task the rat is placed into an arena and its
exploration of two identical objects is measured during a 5-min ex-
posure phase. Next, the rat is removed for a 5-min retention inter-
val and then replaced in the arena for a 3-min test phase. In the novel
object recognition test one new and one familiar object are pre-
sented; for the novel object location test two familiar objects are
presented but one is now moved to a new location (Dix & Aggleton,
1999). Intact memory is reflected by an increased proportion of ex-
ploration time allocated to the novel object, or object in a novel lo-
cation, during the test phase. Equal exploration of the two objects
at test is thought to indicate memory impairments. At retention in-
tervals of 5-min, rats with hippocampal lesions show impaired lo-
cation recognition memory but intact object recognition memory
(Mumby, Gaskin, Glenn, Schramek, & Lehmann, 2002) while rats with
lesions to the peri/post-rhinal cortex show deficits in object recog-
nition memory but intact location recognition memory (Winters,
Forwood, Cowell, Saksida, & Bussey, 2004). However, damage to the
hippocampus can also impair object recognition memory at longer
retention intervals of 24-h (Hammond, Tull, & Stackman, 2004).
Beilharz, Maniam and Morris (2013; Experiment 2) tested
memory on the object location and object recognition tasks in rats
given ad-libitum access to 10% sucrose solution with or without a
high-energy “cafeteria” solid diet. The retention interval in this study
was 5-min. Sucrose-fed rats showed impaired object location
memory, but not object recognition memory after only 5 days on
the diet. Interestingly, this study also found that after 27–29 days
on the diets, sucrose-fed rats showed trends towards elevated hip-
pocampal inflammation and oxidative stress markers, levels of which
correlated negatively with performance on the object location task.
Using an identical test procedure, we recently replicated this result
and found that adult rats fed 10% sucrose or 10.4% maltodextrin so-
lutions ad-libitum had impaired object location but intact object rec-
ognition memory after 18 days on the diets (Kendig, Lin, Beilharz,
Rooney, & Boakes, 2014a; Experiment 3). However, unlike Beilharz
et al. (2013), deficits on object location memory in our study were
not evident at an early test held after 8–9 days on the diets. The
earlier onset of object location memory impairments observed by
Beilharz et al. (2013) may be explained by the added sugar and fat
content provided in the cafeteria diet available to half of the rats
in this study. Using a retention interval of 3-min, Chepulis et al.
(2009) also found no differences in object recognition memory in
rats fed sugar, honey or sugar-free diets for 1 year. As described
earlier, sugar-fed rats in this study appeared to have the poorest
spatial memory in a Y-maze.
The above three studies reported impairments in spatial but not
non-spatial memory in sucrose-fed animals. However, one study by
Jurdak and Kanarek (2009) found that young male rats given 8 weeks
of free access to a 32% sucrose solution showed poorer object rec-
47
ognition memory relative to control rats after a retention interval
of 1-h. The performance of a group given vegetable fat in addition
to chow was intermediate and did not differ significantly from control
or sucrose-fed rats. Fasting blood glucose levels were significantly
elevated in sucrose- and fat-fed rats, and were negatively corre-
lated with the proportion of exploration time on the novel object
for these groups (but not controls). Thus, sucrose can impair object
recognition memory when tested at longer retention intervals which
require intact hippocampal function (Hammond et al., 2004).
Together, this research provides strong evidence that sugar
impairs spatial memory via damage to the hippocampus, a region
known to be integral to spatial learning and memory (e.g. O’Keefe
& Nadel, 1979). Several have suggested that sugar-induced cogni-
tive effects are primarily mediated by changes to insulin function,
such that the insulin resistance produced by sugar consumption in
peripheral tissue may also develop in the hippocampus, which is
densely populated with insulin receptors, to alter cognitive func-
tion (Agrawal & Gomez-Pinilla, 2012; Jurdak et al., 2008; Soares et al.,
2013). Indeed, two studies reviewed above found that sugar-fed
animals exhibited changes to several aspects of insulin signalling
in the hippocampus and that these changes appeared to correlate
with the severity of cognitive impairments and indices of periph-
eral metabolic damage (Agrawal & Gomez-Pinilla, 2012; Soares et al.,
2013). Direct links between fructose-induced insulin resistance in
peripheral tissue and changes in insulin signalling pathways in the
brain have been reported previously (Mielke et al., 2005). However,
changes to glutamatergic and glucocorticoid receptor function in the
hippocampus have been shown and are also likely to contribute
to cognitive deficits (Soares et al., 2013). Sugar may also impair
hippocampal function by increasing oxidative stress and
neuroinflammation, but here there are mixed results: while Soares
et al. (2013) reported no effect of sugar on the inflammatory marker
TNF-α in rats, another study found trends towards increased levels
of TNF-α and IL-1β in sugar-fed rats, with levels of the former cor-
relating strongly with spatial memory impairments (Beilharz et al.,
2013). The fact that Beilharz et al. (2013) observed an increase in
white adipose tissue mass and a slight increase in body weight gain
in sucrose-fed rats, while Soares et al. (2013) found no changes
to body weight, might suggest that the inflammatory response in
hippocampal tissue observed by Beilharz et al. (2013) was a sec-
ondary consequence of obesity.
Instrumental and Pavlovian conditioning
In contrast to the many studies of sugar on memory, there are
few reports of effects of long-term sugar consumption on condi-
tioned behaviour. Two studies have examined the effects of sugar
consumption on discrimination reversal learning. During the first
acquisition phase of this paradigm, animals are given intermixed
presentations of one stimulus that is paired with reward (S+ stim-
ulus, e.g. tone) and another stimulus not paired with reward (S− stim-
ulus, e.g. light). After rats meet some performance criteria (e.g.
correctly responding on a majority of S+ trials and correctly with-
holding responses on a majority of S− trials), in the second rever-
sal phase these contingencies are reversed such that the former S+
is now the S− and the former S− is the new S+. Notably, the hippo-
campus is integral for new learning during this reversal phase, as
shown in both lesion studies (e.g. Winocur & Olds, 1978) and EEG
studies in rats (Sakimoto, Takeda, Okada, Hattori, & Sakata, 2013).
It is thus of great interest to examine the effects of sugar consump-
tion on this non-spatial hippocampal task, in light of the effects of
sugar on other spatial hippocampal tasks discussed above.
Kanoski, Meisel, Mullins, and Davidson (2007) gave adult rats free
or restricted access to high-fat powdered diets formulated with either
22% glucose or 22% sucrose (by weight) as the primary carbohy-
drate source for 90 days. Next, the rats were food-restricted and un-
48 M.D. Kendig/Appetite 80 (2014) 41–54
derwent Pavlovian training for a discrimination reversal learning task,
where all groups learned to discriminate between the S+ and S−
stimuli equally. During reversal sessions, no groups showed signif-
icant discrimination between the new S+ and new S−; however, group
differences were observed in a subsequent “latent reversal” test
where neither stimulus was reinforced. In this extinction test, rats
formerly given free access to the high-fat/glucose diet failed to dis-
criminate between the new S+ and S−, showing equally low re-
sponding to both stimuli. In contrast, the high-fat/sucrose and control
groups showed an appropriate discrimination, and did not differ from
each other. Consistent with the behavioural results, the high-fat/
glucose but not the high-fat/sucrose group showed decreased BDNF
levels in the ventral hippocampus and prefrontal cortex. The authors
speculated that the differential effects of glucose and sucrose on hip-
pocampal BDNF might relate to the higher glycaemic index of the
glucose diet, in conjunction with the extended period of food re-
striction introduced prior to behavioural testing.
A recent study from our laboratory also tested the effects of
sucrose on discrimination reversal learning. The design was broadly
similar to the study of Kanoski et al. (2007), consisting of an 8-week
diet intervention involving free access to 10% sucrose solution (or
water only) and ad-libitum chow, followed by a behavioural testing
phase where rats were food restricted and without access to sucrose
(Kendig, Rooney, Corbit & Boakes, 2014b; Experiment 2). However,
our discrimination reversal task, which was based on the proce-
dure of Sakimoto et al. (2013), included an instrumental compo-
nent whereby a single lever press was required during the S+
presentation for delivery of a food reward. This contrasts the Pav-
lovian procedure used by Kanoski et al. (2007) in which reward was
always delivered to the magazine after the presentation of the S+.
Despite this, and other minor procedural differences, we similarly
found that rats previously fed sugar learned the initial contingen-
cies equivalently to controls, and that there were no group differ-
ences in performance during the discrimination reversal phase or
in subsequent extinction tests (Kendig et al., 2014b). It is thus in-
teresting that these two experiments found no effect of sucrose on
discrimination reversal learning, non-spatial hippocampal-based
tasks, in contrast to the majority of studies reporting sugar-induced
impairments on spatial hippocampal-based tasks.
A third study on the long-term effects of sugar consumption on
instrumental behaviour found that relative to a chow-only control
group, mice that had been fed 15% fructose solution for 3 months,
following termination of this diet intervention and now food-
deprived, made more lever-presses for a pasta food reward on the
fourth and fifth days of operant training (Messier, Whately, Liang,
Du, & Puissant, 2007). This effect could not be related to differ-
ences in glucose tolerance or GLUT5 transporter content, since
fructose-fed and control mice did not differ on these measures. There
were no differences in responding between the high-fructose group
and two other groups fed high-fat or combined high-fat, high-
fructose diets. Although this was interpreted as a positive effect of
fructose on learning and memory, it is not immediately clear how
this operant task involved memory processes. Together, these studies
indicate that while deficits in spatial learning and memory have been
found consistently following sucrose consumption, reliable effects
on simple measures of instrumental behaviour may be more diffi-
cult to detect.
Reward processing
Effects of sugar consumption on reward-related behaviours might
be expected to manifest as heightened food-seeking and ingestive
behaviours, when considering the ways sugar has been shown to
alter brain reward networks. In contrast, animal studies suggest a
more complicated relationship. Since the dopaminergic reward
network is temporarily upregulated during adolescence (Wahlstrom,
White, & Luciana, 2010), several studies have examined the effects
of sugar consumption during this developmental window.
Vendruscolo, Gueye, Darnaudery, Ahmed, and Cador (2010a) ad-
ministered a 16-day period of free access to 5% sucrose solution (or
water only) to adolescent and adult rats, and subsequently mea-
sured motivation to lever-press for saccharin, maltodextrin and
cocaine. Only rats exposed to sucrose during adolescence (during
postnatal day [PND] 30–46) showed reduced motivation to respond
for maltodextrin and saccharin in adulthood. In contrast, exposure
to sucrose in adolescence or adulthood did not influence motiva-
tion to self-administer cocaine. A separate experiment by this group
replicated this result, with rats exposed to 5% sucrose with or without
5% ethanol for 16 days during adolescence showing reduced con-
sumption of saccharin, and reduced preference for ethanol when
tested as adults (Vendruscolo et al., 2010b). However, adolescent
sucrose treatment did not alter ethanol intake when animals could
self-administer intravenously. The lack of effect of sucrose expo-
sure on intravenous cocaine or ethanol self-administration in these
studies parallels a study in rats by Iemolo et al. (2012) in which in-
termittent exposure to a high-sucrose solid diet (2 days/week for
5 weeks) did not alter reward threshold obtained using an intra-
cranial self-stimulation procedure. These results suggest that any
overlap between drug- and food-reward processing networks is
incomplete.
Frazier, Mason, Zhuang, and Beeler (2008) administered young
C57BL/6 mice 4 or 7 weeks of unlimited access to sucrose pellets
in the home cage, and measured body weight, food intake and mo-
tivation towards food rewards in adulthood. Corroborating the results
of Vendruscolo et al. (2010a, 2010b), sucrose-fed mice showed
reduced motivation to work for sucrose in later life, as indicated by
a lower breakpoint for sucrose pellets in a progressive ratio task.
Sucrose-fed mice also showed a preference to eat freely available
solid chow rather than lever-press for sucrose in a concurrent choice
task, and reduced preference for sucrose solution in the home cage.
Although sucrose-fed mice did not gain any excess weight during
sucrose exposure, they rapidly gained excess weight when given free
access to a high-fat, high-sugar diet in later life, suggesting a latent
vulnerability to obesity conferred by early life sucrose consump-
tion. Intermittent exposure to a high-sugar diet exposure has also
been found to reduce the rewarding properties of other foods:
Cottone, Sabino, Steardo, and Zorrilla (2008) fed adult rats a high-
sucrose diet (50% kcal as sucrose) for 2 days/week for 5 weeks, and
found that these rats exhibited reduced motivation to lever-press
for a moderately palatable diet that was itself preferred to regular
chow.
The behavioural profile observed in sucrose-fed rats in the above
experiments – a reduced breakpoint for food rewards and a pref-
erence to eat less palatable, freely available food – is analogous to
the effects of dopamine antagonists on feeding behaviour (Salamone
et al., 1991). These behavioural effects might appear counterintuitive
to the idea that sugar consumption drives unnecessary and exces-
sive food consumption. However, if extended sugar consumption
downregulates the dopamine system, a consequence might be that
only very intense rewards such as palatable foods activate this
network sufficiently to drive behaviour (as is observed after expo-
sure to drugs such as cocaine). Thus, although some of these
behavioural effects manifest as the inhibition of food-seeking
behaviours, they may still have important implications for how sugar
might predispose individuals to poor dietary choices and obesity
over the long term.
Experiments on the effect of sugar exposure on other measures
of dietary behaviour report different results. An early experiment
by Wurtman and Wurtman (1979) found that feeding adolescent
rats diets containing 0%, 12% or 48% sucrose from PND16-30 did not
affect subsequent consumption of these three diets when each were
freely available from PND30-63. A key difference in procedure in this
 M.D. Kendig/Appetite 80 (2014) 41–54
study was that rats could not choose to consume sucrose, as expo-
sure was given in a single solid diet. This suggests that as well as
the timing of access to sugar, providing a choice between sugary and
sugar-free diets may be necessary to produce effects on reward pro-
cessing in later life. This could be achieved either by presenting a
liquid solution or sucrose pellets separately, or by alternating periods
of access to sugar-rich and sugar-free diets.
In contrast to the results of the above experiments is the finding
that rats receiving 1-h/day (5 days/week) access to 10% sucrose with
or without milk during adolescence showed increased consump-
tion of sucrose or sucrose-milk solutions when tested in adult-
hood (Pian, Criado, Walker, & Ehlers, 2009). The fact that access to
sucrose was restricted in this experiment, rather than ad libitum in
most of the previous studies, may explain the elevation in sucrose
preference. This is supported by a study in which adult rats main-
tained on restricted access to 10% sucrose for 4 days per week for
6 weeks made more licks for sucrose solution (indicative of greater
sucrose preference) during a 12-h test, relative to rats fed sucrose
ad libitum (Martin & Timofeeva, 2010). Stronger preferences fol-
lowing intermittent access to sugar is also commensurate with re-
search showing that a sugar-dependent state in rats emerges when
access is restricted and not continuous (e.g. Avena et al., 2008b).
However, continuous access in early life may increase later prefer-
ence for sucrose under some conditions. One study in Wistar rats
found that ad-libitum access to 30% sucrose solution for 3 weeks
during adolescence produced elevated preference for 30% sucrose
over water in adulthood (Sato et al., 1991). Although this experi-
ment did not assess the effects of intermittent access to sugar (control
rats drank water only), results nonetheless suggest that at high con-
centrations, it may not be necessary to provide sugar intermit-
tently to increase sucrose preference.
As well as considering how sugar can alter preferences for, and
consumption of foods, it is pertinent to examine whether sugar
affects the flexibility of an animal’s food-seeking behaviours. The
outcome devaluation paradigm is a behavioural assay that exam-
ines how an animal’s instrumental responding for an outcome
(usually a food reward, e.g. pellets) is sensitive to changes in the value
of that reward (Adams & Dickinson, 1981). This is achieved by de-
valuing the outcome – either by feeding it to satiety or by pairing
it with illness using lithium chloride – before testing the magni-
tude of the instrumental response in an extinction test (Adams, 1982).
Behaviour is considered to be goal-directed if responding is reduced
following outcome devaluation. Conversely, continued respond-
ing following outcome devaluation is indicative of habitual behaviour
that is less sensitive to changes in outcome value (Dickinson, 1985).
Control rats typically show goal-directed responding after limited
training, and progress to habitual responding after extended train-
ing (Adams, 1982) and drugs such as amphetamine can accelerate
this loss of goal-directed control over behaviour (Nelson & Killcross,
2006).
We have examined the effects of sucrose on habit formation using
the outcome devaluation paradigm in two experiments. In the first
(Kendig et al., 2013), rats were given 28 days of restricted access (2-
h/day) to 10% sucrose or 0.1% saccharin solutions. After removing
access to sweet solutions and introducing food restriction, rats
learned to lever-press for pellets in twice-daily training sessions.
Outcome devaluation tests were held at repeated intervals through-
out this instrumental training to assess changes in the sensitivity
to devaluation over time. Sucrose-fed rats lost sensitivity to deval-
uation treatment more quickly, since at the third set of tests test
lever pressing was equivalent in devalued and nondevalued tests
for sucrose-fed rats, whereas controls still showed sensitivity by
making fewer presses after reinforcer devaluation. This is sugges-
tive of an accelerated shift from goal-directed to habitual respond-
ing in sucrose-fed rats. Interestingly, in this study rats given sucrose
or saccharin solutions during adolescence did not show sensitivity
49
to devaluation at the first test. Adolescent rats can show sensitiv-
ity to devaluation with no diet or other manipulation (Naneix,
Marchand, Di Scala, Pape, & Coutureau, 2012); thus, our result might
suggest that repeated intermittent exposures to any sweet taste
during adolescence (caloric or not) alters the ways that rewards are
appraised in adulthood. This would be generally consistent with the
aforementioned studies that provided sweet solutions ad-libitum
during adolescence (Frazier et al., 2008; Vendruscolo et al., 2010a,
2010b).
The second experiment to assess the effects of sugar on habit for-
mation gave adult male albino and hooded Wistar rats 8 weeks of
free access to 10% sucrose solution or water only, with behavioural
testing conducted after sucrose exposure when rats were food de-
prived (Kendig et al., 2014b; Experiment 1). Unlike our earlier study,
sucrose did not accelerate habit formation and all rats remained sen-
sitive to outcome devaluation over time. The fact that sucrose was
provided ad-libitum and not intermittently in this study may explain
why no effect on habit formation was observed. This interpreta-
tion is supported by recent data showing that habitual control over
behaviour is accelerated by intermittent but not continuous access
to sweetened-condensed milk (Furlong, Jayaweera, Balleine, & Corbit,
2014). Despite no loss of sensitivity to outcome devaluation, in our
study we found that the pre-feeding treatment had the smallest effect
on instrumental performance in sucrose-fed albino rats, such that
this group continued to lever-press at a greater rate during extinc-
tion tests relative to other groups. We interpreted this as insensi-
tivity to the shift in motivation produced by the pre-feeding
devaluation treatment, an effect which may be explained by the
excess weight gain in these sugar-fed albino rats.
The neural mechanisms underpinning these behavioural effects
are largely unclear. When considering that dopaminergic and
opioidergic receptor signalling is altered in sugar-dependent rats
(Colantuoni et al., 2001, 2002), changes to these neurochemical
systems may also underlie behavioural deficits in sugar-fed rats that
are not sugar dependent. Respectively, dopamine and opioid trans-
mission are thought to regulate incentive motivation towards, and
the hedonic appraisal of, rewards (Kenny, 2011). It follows that the
behavioural effects in sugar-fed rats reported above might be at-
tributable to changes in these two distinct systems. As a brief
example, a reduced breakpoint to lever-press for food rewards in
sucrose-fed rats might be explained by changes to dopamine trans-
mission (e.g. by the blunted dopamine response and consequent re-
duction in incentive motivation to respond); opioid transmission (e.g.
diminishing the hedonic value of the food reward) or interactions
between these systems. Performance on behavioural tasks may of
course also be modulated by other physiological systems, such as
the release of satiety peptides during feeding, that may interact with
brain reward processing. There is thus clear scope to improve un-
derstanding of how sugar consumption alters reward-related
behaviour. In particular, it will be important to examine how sugar
affects the functioning of these reward systems in paradigms that
do not induce sugar dependency.
The following conclusions can be drawn from the research re-
viewed in this section. Providing animals with either continuous or
restricted access to sugar during adolescence can reduce the mo-
tivation to work for food rewards later, a result which in some in-
stances is coupled with overconsumption of freely available, palatable
food. Sugar consumption in adolescence or adulthood does not
appear to alter drug self-administration or cranial self-stimulation.
Although much of this research has focused on younger animals,
the extent to which effects of sugar on reward-related behaviours
are specific to adolescence (e.g. Vendruscolo et al., 2010a), or simply
differ between adolescent and adult animals (e.g. Kendig et al., 2013)
remains largely unclear. This calls for further investigation of the
effects of sugar consumption across the life span. Both continuous
and intermittent access to sugar can alter reward-related behaviour;
50 M.D. Kendig/Appetite 80 (2014) 41–54
however, these two forms of access have rarely been directly
compared.
Anxiety and depression-like behaviour
Long-term effects on anxiety
Cao et al. (2007) reported that in a mouse model of Alzheim-
er’s disease, 25 weeks of exposure to 10% sucrose had no detect-
able effect on anxious behaviour as measured in the Elevated Plus
Maze, Open Field, and T-maze tests. Hendley et al. (1987) found that
spontaneous activity in a brightly-lit, novel cage was not altered by
overnight or chronic (14–18 days) access to sucrose pellets in ad-
dition to chow. However, in female spontaneously hyperactive
Wistar–Kyoto rats, overnight feeding of sugar pellets disrupted ha-
bituation to a novel cage on the next day, while chronic sugar feeding
rendered rats more sensitive to changes in colour and illumina-
tion in an open field, suggestive of greater distractibility. After a
1-year diet intervention with 7.9% sucrose, 10% honey or no sugar
mixed into the solid diet, Chepulis et al. (2009) found that honey-
fed rats showed reduced anxiety in the Elevated Plus Maze rela-
tive to sucrose-fed rats, which did not differ from controls. Metabolic
data at cull, published separately by Chepulis and Starkey (2008),
showed that as well as reduced weight gain, honey-fed rats had lower
percent body fat and blood sugars, and higher HDL cholesterol levels
than sucrose-fed rats. Rats fed sucrose gained more weight and de-
posited more body fat than honey-fed and control groups.
Although this review is concerned with evidence for lasting effects
of sugar on behaviour and cognition, it is important to note that acute
withdrawal from diets high in sucrose can induce acute anxiety and
depression-like behaviours. For example, rats given 12-h intermit-
tent access to 10% sucrose solution for 28 days exhibited height-
ened anxiety on the Elevated Plus Maze (EPM) after a 36-h fast
(Avena et al., 2008a). Rats given this intermittent access schedule
for 28 days also show reduced conditioned suppression after 1 and
28 days of abstinence, as indexed by a failure to significantly reduce
lever-pressing for sucrose solution during the presence of a tone
stimulus paired with shock (Maracle, 2012, unpublished thesis). Other
groups have reported similar results using longer cycling periods.
For example, rats given intermittent access to a high-sucrose diet
(2 consecutive days per week; 50% kcal in solid diet) showed in-
creased anxiety in the EPM and defensive withdrawal tests after 8
and 9 weeks on the diet cycle, respectively (Cottone, Sabino, Steardo,
& Zorrilla, 2009). Iemolo et al. (2012) found that rats given the same
high-sugar/chow diet cycle for 7 weeks showed greater immobili-
ty on the Forced Swim Test (suggestive of a depressive phenotype)
and decreased preference for 0.8% sucrose (suggestive of anhedo-
nia) relative to chow-fed controls, when testing while sugar rats did
not have access to sugar. There was no effect of diet when testing
while the high-sugar diet was available, confirming that this effect
was an acute one of withdrawal rather than a lasting behavioural
deficit. In summary, the available research indicates that, except in
genetically vulnerable strains or under conditions of acute with-
drawal, consuming sugar does not lead to lasting alterations in
anxious or depressive behaviour.
Summary and future directions
Current evidence indicates that sugar consumption can induce
lasting changes on a range of behavioural and cognitive measures.
A clear majority of studies have found that animals fed sugar perform
more poorly on behavioural and cognitive tasks than control animals
not fed sugar. However, these effects do appear to vary according
to the nature of the task. Spatial learning and memory have been
most consistently impaired following consumption of sugar solu-
tions, while the few studies to test other measures of instrumen-
tal and Pavlovian conditioning have not found robust effects. Sugar
consumption can alter brain reward circuitry to change the way in
which animals earn, consume, and prefer different foods, and these
effects may be heightened when sugar is provided during adoles-
cence. Sugar consumption does not appear to produce lasting changes
to anxiety or mood, except for circumstances where access to sugar
is abruptly withdrawn.
When does sugar intake become harmful?
It is important to move beyond the general conclusion that sugar
can impair behaviour and cognition to form directions for future re-
search. Amongst these, a priority is to establish at what level of intake
and under what circumstances sugar consumption becomes harmful.
While this is currently unknown, aspects of the studies reviewed
here provide some insights. An initial observation is that impair-
ments have been found using experimental methods that vary widely
in terms of how, how much, and for how long sugar is provided to
animals. Importantly, effects on cognition and behaviour do not
appear to be driven by any one of these measures; that is, the con-
centration of sugar solution; the total duration of access; or whether
access is continuous or restricted. It is noteworthy that effects on
behavioural and cognitive measures do not appear to depend on the
latter factor, since it is an integral determinant of whether sugar ex-
posure elicits a dependent state in rats (Avena et al., 2008b). This
directs future research to examine whether “sugar-dependent” rats
show long-term changes to other cognitive processes.
Population data on human dietary patterns commonly express
sugar consumption in terms of the total proportion of total energy
consumed as sugar. Recent data indicate that for a majority of Ameri-
cans, added sugar contributes between 5% and 20% of total energy,
while 12.5% draw 25% or more calories from sugar and for 5.9% of
the population this proportion is above 30% (Marriott et al., 2010).
Calculating this measure in experiments using animals provides a
basis on which to compare with human data, albeit on a crude level
that overlooks physiological and metabolic differences between
people and animals. As can be seen in Table 1 (see “percent kcal from
sugar” column), sugar contributed anywhere from ~5% to ~70% of
total energy in these animal studies reviewed here (with the largest
determinants of this proportion being the concentration of sugar
solution and whether access was restricted or ad-libitum). Impor-
tantly, the available data do not suggest that there is a threshold of
sugar intake above which behaviour or cognition is impaired. Indeed,
experiments have found sugar-induced behavioural impairments at
levels of intake that are comparable to those in people (e.g. 7.9%,
Chepulis et al., 2009; ~12%, Kendig et al., 2013; ~21%, Vendruscolo
et al., 2010b).
In summary, it does not appear possible on the basis of exist-
ing evidence to identify a single “safe” level of sugar consumption.
Rather it is likely that effects on behavioural measures depend on
interactions between the amount of sugar ingested, rat strain and
age, and other procedural factors. Furthermore, since sugar con-
sumption may impair aspects of cognition and behaviour via nu-
merous mechanisms, any threshold levels for consumption are likely
to vary according to which aspect of cognition is being consid-
ered. Nonetheless, parametric studies manipulating the propor-
tion of sugar in the diet and the duration of access could help clarify
how much sugar an animal can ingest (and for how long) before
aspects of behaviour or cognition are compromised.
Relationship between cognitive and metabolic effects
It is also relevant to consider the degree to which cognitive effects
of sugar can be related to or separated from peripheral metabolic
ones. Since metabolic studies in rats have shown that the propor-
tion of sugar in the diet directly predicts the time of onset of met-
 M.D. Kendig/Appetite 80 (2014) 41–54
abolic impairment (Pagliassotti & Prach, 1995; Pagliassotti, Prach,
Koppenhafer, & Pan, 1996), it is highly relevant to examine whether
cognitive and behavioural deficits are predictable in similar ways.
Arguably the most important metabolic change that can obscure the
interpretation of results is whether or not sugar has accelerated
weight gain. This has important implications for whether any
behavioural and cognitive effects can be attributed to the diet di-
rectly or to secondary consequences of obesity. Several of the studies
reviewed here show effects of sugar in the absence of changes to
total energy intake and body weight. Additionally, impairments have
been found to persist long after access to sugar is withdrawn and
when metabolic damage in sugar-fed rats has resolved (e.g. Kendig
et al., 2013). However, it is not yet clear whether sugar can
alter behaviour or cognition if metabolic function is never
compromised.
Whether or not sugar consumption has caused metabolic changes
may have implications for the mechanisms underlying sugar-
induced cognitive changes. For example, the onset of obesity may
also alter levels of satiety peptides such as leptin, ghrelin, and neu-
ropeptide Y (Lindqvist et al., 2008; Lindqvist, de la Cour, Stegmark,
Hakanson, & Erlanson-Albertsson, 2005), which may in turn alter
how food rewards are appraised. Studying the effects of sugar on
the functioning of these homeostatic systems – with or without
obesity – will be important in understanding what underlies effects
on behavioural tasks that use food reinforcers. The onset of obesity
can also present procedural problems. To take an extreme example,
in one long-term study, an unintended confound produced by excess
weight gain in sugar-fed rats was that data from an Elevated Plus
Maze test after 12 months on the diet had to be discarded due to
the inability of many rats to turn around in the closed arms of the
maze (Chepulis et al., 2009).
Implications for human diets
Inferring putative effects of sugar on behaviour and cognition in
people is complicated by the several ways in which the experi-
ence of animals consuming sugar differs from the human condi-
tion. First, the proportion of energy derived from sugar in the present
animal studies in many cases exceeds average levels of consump-
tion in people. However, another important point is that very few
of the animal studies reviewed here examined the effects of sugar
over a truly “long-term” period. For most people sugar consump-
tion begins in early life and continues (with variability across time
and between individuals) over a lifetime. In contrast, animal studies
commonly cease access to sugar after a period of weeks or months
– an incomparable period of time even when considering the shorter
lifespan of rodents. (An exception to this is the study of Chepulis
et al., 2009 in which rats remained on test diets for a year.) Thus,
the higher proportion of energy provided by sugar in some animal
studies is counteracted by the shorter window of time in which sugar
is available. Even studies that provide a greater-than-average pro-
portion of calories through sugar are still likely to capture a subset
of the human population with high levels of consumption.
A related concern is that appetitive paradigms using food rewards
often involve ceasing the diet manipulation in order to induce the
mild hunger necessary for rats to perform behavioural tasks ade-
quately. While this approach reduces the possibility that acute sugar
consumption might alter performance in the task (e.g. by chang-
ing the palatability of another food reinforcer), and taste prefer-
ences can be compared across groups, it is nonetheless unclear how
introducing food restriction washes out effects of the initial diet ma-
nipulation in these instances. A study that examines metabolic and
behavioural outcomes after systematically manipulating the removal
of sugar and removal of chow following a diet intervention could
be important.
51
It is also important to acknowledge that in most of these studies
sugar represents the only palatable food item in a diet that con-
sists otherwise of chow and water. This is in contrast to a majority
of the human population who have abundant access to a wide range
of palatable foods high in sugar, fat, or both. Two questions that
follow from this observation are (a) whether sugar would exert
similar cognitive effects in instances where it was not the only pal-
atable option in an animal’s diet, and (b) whether other palatable
foods or solutions might produce similar changes in behaviour. Es-
tablishing the specific nature of any cognitive effects of sugar in
people would be difficult since these would likely co-occur to a high
degree with cognitive problems resulting from obesity (Smith, Hay,
Campbell, & Trollor, 2011). Delineating the effects of sucrose from
other dietary components would be important, since other animal
data show pronounced behavioural effects following restricted access
to high-fat, or combined high-fat/high-sugar foods (Corwin, Avena,
& Boggiano, 2011).
Another important question for future research is to examine
which forms of sugar carry the greatest risk of harm. Clarifying the
role of fructose seems particularly important, since some evi-
dence suggests fructose poses particular risk to metabolic health
(Aeberli et al., 2011; Kanarek & Orthen-Gambill, 1982; Lustig, 2013)
yet others claim these effects are overstated (Tappy & Mittendorfer,
2012; White, 2013). Further, animal literature on the cognitive effects
of fructose shows mixed results ranging from detrimental (Agrawal
& Gomez-Pinilla, 2012) to neutral (Kanoski et al., 2007) or appar-
ently positive (Messier et al., 2007). Since recent work suggests that
both fructose-containing (sucrose) and fructose-free (maltodextrin)
sugar solutions can produce memory impairments in rats (Kendig
et al., 2014a), further comparisons between different monosaccha-
rides and other caloric solutions on behavioural and cognitive tasks
are needed.
Finally, since sugar contains both calories and a sweet, pleasur-
able taste, future studies could delineate the effects of these
components by comparing the behavioural effects of consuming a
non-sweet caloric solution versus a non-caloric sweet solution.
Indeed, the taste alone of sucrose solution can stimulate dopa-
mine release in the nucleus accumbens, as shown using sham-
feeding procedures (Avena, Rada, Moise, & Hoebel, 2006).
Comparisons of the cognitive effects of nutritive versus non-
nutritive sweeteners would complement existing data on the met-
abolic effects of artificial sweeteners. For example, one theory
(Swithers, 2013) proposes that excessive consumption of non-
nutritive sweeteners increases the risk of weight gain by disrupt-
ing a pre-existing association between sweet tastes and calories.
In conclusion, the implications of the present experiments
are of concern in light of the continuing global increase in
sugar consumption that is driven largely by rising intakes of
sugar drinks. There is still considerable work needed to better un-
derstand the physiological and neural mechanisms that underlie
sugar-induced impairment of these processes, and the interac-
tions between them. As well as continued study of the experimen-
tal conditions that produce effects, identifying interventions to restore
or prevent sugar-induced behavioural and cognitive impairments
will be equally important. Nonetheless, the research reviewed here
provides support for the notion that consumption of sugar drinks
should be limited to protect against cognitive as well as metabolic
harm.
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