Alcohol and Alcoholism, 2017, 52(5) 610–616

doi: 10.1093/alcalc/agx040
Advance Access Publication Date: 17 June 2017
Article

Article

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Differential Effects of Alcohol on Memory
Performance in Adolescent Men and Women
with a Binge Drinking History
Concepción Vinader-Caerols1,*, Andrew Talk2, Adriana Montañés1,
Aránzazu Duque1, and Santiago Monleón1
1
Department of Psychobiology, University of Valencia, Blasco Ibáñez, 21, 46010 Valencia, Spain, and 2Department
of Psychology, University of New England, Armidale, NSW 2351, Australia

*Corresponding author: Tel: +34-96-386-46-52; Fax: +34-96-386-46-68; E-mail: concepcion.vinader@uv.es

Received 11 January 2017; Revised 17 May 2017; Accepted 31 May 2017

Abstract
Aims: Binge drinking (BD) is characterized by intermittent consumption of large quantities of alco-
hol in short periods. This pattern of drinking is prevalent among adolescents, and has been asso-
ciated with undermined learning and memory ability. This study investigates the relationships
between a history of BD and the effects of acute exposure to alcohol on learning and memory per-
formance in adolescent men and women.
Methods: A high, acute dose of alcohol or control refreshment was administered to a sample of
172 adolescent undergraduate students, some of which had a history of BD and others of which
had refrained from alcohol consumption. Subsequently, immediate visual memory (IVM) and
working memory (WM) was measured according to the Wechsler Memory Scale in females and
males with different BAC (Experiment 1) and similar BAC (Experiment 2).
Results: In both experiments, IVM was reduced after acute alcohol consumption and there was no
significant main effect of Drinking Pattern. Furthermore, an effect of cognitive alcohol tolerance on
IVM was observed in women but not in men. WM was not affected by alcohol, but a gender differ-
ence was evident in that performance was superior in men than in women.
Conclusions: In adolescents, IVM is more sensitive than WM to impairment by alcohol, and
women are more vulnerable to the neurotoxic effects of alcohol than men, since the cognitive tol-
erance effect of alcohol on IVM develops in BD women but not in BD men. These findings empha-
size the need to investigate the neurotoxic effects of alcohol in adolescent women.
Short summary: In adolescents, immediate visual memory (IVM) is more sensitive than working
memory to impairment by alcohol, and women are more vulnerable to the neurotoxic effects of
alcohol than men, because the cognitive tolerance effect of alcohol on IVM develops in binge
drinking (BD) women but not in BD men.

INTRODUCTION Alcoholism defines BD as a pattern of drinking that brings a per-

Alcohol is one of the most widely consumed psychoactive substances
in the world, especially among young people and adolescents (Hibell
et al., 2007; Chavez et al., 2011). Among Spanish 14- to 18-year-
olds, 32.2% develop a pattern of alcohol consumption known as
binge drinking (BD). The National Institute on Alcohol Abuse and
son’s blood alcohol concentration (BAC) to 0.08 g per cent or
above (NIAAA, 2004). This pattern involves the intake of large
quantities of alcohol in a short time (about 2 h), followed by a peri-
od of abstinence, with the repeated alternation between intoxica-
tion and withdrawal being particularly deleterious for the brain

© The Author 2017. Medical Council on Alcohol and Oxford University Press. All rights reserved. 610
Alcohol and Alcoholism, 2017, Vol. 52, No. 5
(Maurage et al., 2012; Petit et al., 2014). Men typically show a
higher prevalence of alcohol consumption than women, but in
Spain, the incidence of alcohol consumption in 14–18-year-old
adolescents is higher among females than males. With respect to
BD, this pattern is similar in both sexes in 14–16-year-old adoles-
cents and is more widespread among men than women in the age
range of 17–18 years (OED, 2016).
Animal (Guerri and Pascual, 2010; Van Skike et al., 2012;
Alfonso-Loeches et al., 2013) and human (Caldwell et al., 2005; Liu
et al., 2010; Squeglia et al., 2012) studies show that females are
more susceptible than males to the effects of alcohol, which can lead
to a reduction of prefrontal cortical and hippocampal volume (De
Bellis et al., 2000, 2005) and related cognitive deficits, such as
undermined reward-related learning, spatial memory, and working
memory (WM; Squeglia et al., 2012; Ozsoy et al., 2013). Alcohol-
related cognitive impairments are more pronounced when there is a
pattern of binge drinking and when consumption takes place during
adolescence (Peeters et al., 2014).
During adolescence, important physical, social and cognitive
skills are acquired and the brain undergoes considerable structural
and functional changes associated with the development of these
skills (Blakemore, 2008). Any disruptive effects of alcohol on learn-
ing and memory abilities have a particularly deep impact during this
period and can last through adulthood. Moreover, due to its greater
plasticity, the adolescent brain appears to be particularly susceptible
to experience-dependent learning processes associated with con-
sumption of alcohol that can lead to tolerance and addiction (Nixon
and McClain, 2010).
There is evidence suggesting that female adolescents are espe-
cially vulnerable to the neurotoxic effects of alcohol on cognition
(Caldwell et al., 2005; Squeglia et al., 2011; Alfonso-Loeches et al.,
2013). Thus, we consider them to be a potential risk population in
which the consequences of alcohol abuse, such as cognitive effects,
need to be studied in a more exhaustive manner, as other authors
have already suggested (López-Caneda et al., 2014). In the current
study, we explored alcohol tolerance in male and female adoles-
cents, evaluating gender differences and potential relationships
between a BD pattern and the effects of acute alcohol exposure on
learning and memory. This interaction needs to be studied, because
some long-term effects of repeated alcohol exposure in adolescents
(such as alcohol tolerance or damaged cognitive abilities) are only
observed, or can be observed more readily, following an acute dose
of alcohol.
It is known that tolerance can be developed early in adolescents
and young adults without alcohol use disorder (AUD) (Saha et al.,
2006; Schuckit et al., 2008). Considering the scarcity of studies that
evaluate the phenomenon of tolerance in healthy adolescents and
the potential vulnerability of females to the neurotoxic effects of
alcohol, we hypothesized that: (a) we would observe an interaction
between drinking pattern and an acute alcohol dose, in which binge
drinkers would perform better in memory tasks than refrainers
when given alcohol (as they would have developed alcohol toler-
ance) and binge drinkers would perform worse than refrainers after
being given the control drink (as their memory would have been
damaged) and (b) gender differences would be observed in these
effects, being more pronounced in women than men. Two experi-
ments were carried out with these objectives in mind; the first one in
men and women separately, with different BACs; and the second
one in a selection of men and women with similar BAC, which
allowed us to study the effect of gender.
611
METHODS
Subjects
Undergraduate students from the University of Valencia, Spain,
filled in a self-report questionnaire about consumption of drugs, fre-
quency and level of alcohol consumption, hours and quality of sleep,
and physical and psychological health. One hundred and seventy-
two subjects (79 males and 93 females) were recruited for the study
based on strict inclusion and exclusion criteria. The following inclu-
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sion criteria were used: 18–19 years old, a healthy body mass index
(mean in men: 22.91 ± 0.97, mean in women: 21.54 ± 0.24) and
good health (without major medical problems). The exclusion cri-
teria were as follows: taking medication; a history of mental disor-
ders (diagnosed by a health professional according to DSM criteria);
an irregular sleep pattern (non-restorative sleep and/or irregular
schedule); having consumed, even sporadically, any drug (apart
from alcohol) or having a history of substance abuse, including caf-
feine, tobacco and alcohol; and having first-degree relatives with
alcoholism problems. A telephone interview of approximately 15
minutes was conducted with each subject in order to confirm the
information provided in the self-report and to fix the date and time
of the test.
Selected students were invited to participate in the current study
if they had reported refraining from alcohol consumption (or very
sporadic consumption) or a history of alcohol use classified as a BD
pattern according to the NIAAA criteria for Spain (see López-
Caneda et al., 2014). The mean age at onset of alcohol use was
15.9 ± 0.23 for sporadic consumers and 14.6 ± 0.11 for binge drin-
kers. Participants were classified as binge drinkers if they had drunk
six or more standard drink units (SDU = 10 g of alcohol) of distilled
spirits (alcohol content ≥40 vol.%) in the case of men or five or
more SDU in the case of women on a minimum of two or three
occasions a month throughout the 12 months prior to the survey.
Participants were classified as refrainers if they had never previously
drunk alcoholic drinks or had drunk very sporadically (less than
one SDU on less than 3 occasions per year; e.g. 250 ml of beer, per
occasion) since the onset of their alcohol use.
Informed consent was obtained from all participants and the
study was conducted in accordance with the guidelines for human
experimentation of the Ethics Committee of the University of Valencia
(ethical authorization number: H1327668013118) and with those of
the Helsinki Declaration. Participants were told to abstain from drink-
ing alcohol and performing heavy physical exercise on the evening/
night prior to the experiment, and all subjects were instructed to
follow their normal sleep patterns and usual meal routine at least
two hours before the experimental session.
Male and female alcohol-refraining and BD subjects were allocated
to one of two groups that received either alcohol or a control drink
during the study. Allocations was random, except for subjects who
had never previously drunk alcohol, who were assigned to the control
drink group for ethical reasons, while some of the subjects who gener-
ally refrained from alcohol but had reported previously having at least
one drink were assigned to the group that received alcohol. The male
subgroups consisted of 11–23 participants each, while the female sub-
groups consisted of 11–27 participants each. In the female subgroups,
data regarding menstrual cycle were registered in the self-report and
during the telephone interview, and cycle phase was taken into
account in the test in order to counterbalance this variable.
The characteristics of the study population are summarized in
Table 1.
612 Alcohol and Alcoholism, 2017, Vol. 52, No. 5

Table 1. Characteristics of the study population

Occasional consumers (n = 35) Binge drinkers (n = 96)

Men Women Men + women Men Women Men + women

(n = 17) (n = 18) (n = 35) (n = 45) (n = 51) (n = 96)

Age at first alcohol consumption 15.9 ± 0.29 15.8 ± 0.29 15.9 ± 0.20 14.7 ± 0.16&&& 14.6 ± 0.15&&& 14.6 ± 0.11+++
Mean number of occasions per month 0.2 ± 0.08 0.2 ± 0.04 0.2 ± 0.04 2.7 ± 0.12&&& 2.6 ± 0.12&&& 2.6 ± 0.12+++
Mean number of drinks per occasion 0.7 ± 0.2 0.8 ± 0.15 0.8 ± 0.15 6.8 ± 0.24&&& 6 ± 0.27*&&& 6.4 ± 0.19+++

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Mean number of BD episodes per month NA NA NA 2.5 ± 0.16 2.3 ± 0.17 2.3 ± 0.12
Mean duration of BD pattern (in months) NA NA NA 13 ± 0.91 11.4 ± 0.33 12.1 ± 0.46
until the beginning of experiment

Refrainers + occasional consumers (n = 76) Binge drinkers (n = 96)

Men Women Men + women Men Women Men + women

(n = 34) (n = 42) (n = 76) (n = 45) (n = 51) (n = 96)

Mean number of stimulant drinks: coke, 0.4 ± 0.11 0.5 ± 0.11 0.5 ± 0.08 0.8 ± 0.15 0.7 ± 0.11 0.7 ± 0.09
tea or coffee/day
Smoker: no/yes 34/0 42/0 75/0 45/5 51/8 51/8
BMI 23.2 ± 0.59 21.6 ± 0.37* 22.3 ± 0.34 22.7 ± 0.34 21.5 ± 0.33* 22.1 ± 0.24
STAI trait 30.9 ± 5.14 30.6 ± 3.62 30.8 ± 3.04 24.3 ± 3.29 28 ± 3.53 26.3 ± 2.42
STAI state 22.9 ± 2.41 30.8 ± 4.09 27.2 ± 2.52 27 ± 2.59 30.9 ± 2.8 29.1 ± 1.92

The results are expressed as number or mean ± SEM for refrainers, occasional consumers and binge drinkers.
NA: not applicable; STAI: State and Trait Anxiety Inventory.
*P < 0.05: Statistically significant difference between men and women in the same group according to Student’s t-tests.
&&&
P < 0.001: Statistically significant difference between binge drinkers and occasional consumers in the same sex according to Student’s t-tests.
+++
P < 0.001: Statistically significant difference between binge drinkers and occasional consumers according to Student’s t-tests.

Tests and apparatus
A digital automatic blood pressure monitor (M10-IT, OMRON,
Spain) was used to measure systolic and diastolic blood pressure
and heart rate in all the subjects.
An alcoholmeter (Alcoquant® 6020, Envitec, Germany) was
employed to measure the concentration of alcohol in the air exhaled
before and after intake of a drink.
The Alcohol Use Disorders Identification Test (AUDIT) (Saunders
et al., 1993) was employed to measure problematic use of alcohol
among the subjects. The AUDIT consists of 10 questions that evalu-
ate the quantity and frequency of alcohol intake and alcohol-related
behaviours and consequences. It uses a range of 0–40, in which a
score of 8 or more indicates a problematic use of alcohol. A higher
score is related to greater severity of problematic drinking.
Immediate visual memory (IVM) and WM were both assessed
using the Wechsler Memory Scale 3rd Edition (WMS-III; adapted ver-
sion for Spanish population) (Wechsler, 2004). The IVM subscales
require the respondent to recognize faces and remember scenes. The
WM subscales require the respondent to put letter-number sets in order
and to reproduce visual-spatial sequences. Subjects’ scores on the WM
and IVM scales were transformed into centiles according to the sub-
ject’s age.
in the form of vodka (120 ml) mixed with the refreshment. The sub-
jects were instructed to consume their drink within a period of
20 min. After finishing the drink, all subjects rinsed their mouths
with water and waited for 20 min.
Following the treatment and wait interval, the concentrations of
alcohol in exhaled air were measured. Blood pressure and heart rate
were then measured to ensure they were in the normal range (no more
than 14 mmHg systolic and 9 mmHg diastolic and less than 100
bpm). Subjects then performed the IVM and WM tests, and alcohol
concentration was measured once again. All the tests were performed
between 4:00 pm and 8:00 pm and members of the groups that
received alcohol remained on the premises until their alcohol concen-
tration dropped to legal limits for driving. The measures of the con-
centrations of alcohol in exhaled air were transformed to BAC.
In Experiment 1, BAC was 0.00 g/l for men and women before
the alcoholic drink, and 0.33 ± 0.08 g/l for men and 0.5 ± 0.02 g/l
for women after drinking and during the memory tests. This differ-
ence in BAC between men and women was statistically significant
(F(1,67) = 41.5, P < 0.001). A counterbalanced selection of men and
women with similar BAC (0.38 ± 0.08 g/l) without statistically sig-
nificant differences (F(1,42) = 3.54, ns) participated in Experiment 2.

Procedure
First, alcohol concentration was measured using the alcoholmeter in
the subjects with a history of BD pattern to ensure that they had not
consumed alcohol previously on the day in question. Alcohol use by
the BD subjects was then assessed using the AUDIT test (mean score:
7.1 ± 0.45 in men and 6.3 ± 0.35 in women). None of the subjects
was classified as alcohol-dependent. Each subject then received
330 ml of a lime- or orange-flavoured refreshment. The subjects
assigned to the alcohol groups were administered 38.4 g of alcohol
Statistical analyses
Data for men and women were analysed separately (Experiment 1)
or together (Experiment 2). Body mass index (BMI) was included as
a covariate in each analysis to control for the effect of values that
varied among the subjects. The data were subjected to parametric
analysis after checking that they met the criteria for normality and
homogeneity of variances. The data were also checked to confirm
that the assumptions for analysis of covariance (ANCOVA) were
met. An ANCOVA was performed for each measure (IVM and
WM) for men and women separately (Experiment 1) or together
Alcohol and Alcoholism, 2017, Vol. 52, No. 5 613

(Experiment 2). Each analysis contained the between-subjects factors
‘Drinking Pattern’ (refrainers, binge drinkers) and ‘Treatment’ (con-
trol drink, alcohol) as independent variables and BMI as a covariate.
When their interaction was statistically significant, pairwise compar-
isons were carried out. All analyses were performed using the ‘SPSS’
Statistics software package, version 22.0 for Windows (IBM, 2013).
RESULTS
In women (see Fig. 2), administration of the alcoholic drink led
to lower IVM scores than administration of the control drink
(F(1,88) = 18.206, P < 0.001). There was no significant main effect
of Drinking Pattern on IVM performance (F(1,88) = 0.005, ns).
However, the interaction between Treatment and Drinking Pattern
was significant (F(1,88) = 7.19, P < 0.01). Pairwise comparisons
indicated that subjects with a history of refraining from drinking
had lower scores when given alcohol than when given the control

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A summary of descriptive statistics for IVM and WM in Experiments
1 and 2 is presented in Table 2.
Experiment 1: Effects of a high dose of alcohol on
performance of memory tests in adolescent males (BAC:
0.33 ± 0.08 g/l) and females (BAC: 0.5 ± 0.02 g/l) with a
history of BD or having refrained from alcohol use
Immediate visual memory
In men (see Fig. 1), IVM was lower in subjects given alcohol than
in those given the control drink (F(1,74) = 7.119, P < 0.01). There
was no significant main effect of Drinking Pattern on IVM per-
formance (F(1,74) = 0.002, ns). The interaction between Drinking
Pattern and Treatment was also not statistically significant (F(1,74) =
0.646, ns).
Table 2. Summary of descriptive statistics for IVM and WM
drink (F(1,39) = 30.557, P < 0.001), but there was no significant
difference among binge drinkers between those given alcohol versus
the control drink. However, among the women given alcohol, binge
drinkers had higher scores than refrainers (F(1,39) = 4.680, P <
0.05). This suggests that tolerance develops in binge drinkers so that
the effect of alcohol on their IVM performance after drinking alco-
hol is less than that seen in refrainers. Finally, binge drinkers given
the control drink obtained lower scores than refrainers given
the control drink, but this effect was only marginally significant
(F(1,48) = 3.733, P = 0.053), suggesting an association between BD
and reduced performance in this task, even in the absence of alcohol.
Working memory
In men, WM was not significantly different between subjects given the
control drink and those receiving alcohol Treatment (F(1,74) = 1.285,
ns), and Drinking Pattern did not have a statistically significant effect
(F(1,74) = 0. 61, ns). The effect of the interaction between Drinking

Experiment 1

Male subgroups IVM WM

BAC 0.33 ± 0.08 g/l

Refraining-Control drink 40.75 ± 6.79 58.24 ± 5.75

Refraining Alcohol 30.62 ± 7.58 48 ± 6.99
BD-Control drink 44.73 ± 5.66 51.37 ± 4.99
BD-Alcohol 24.75 ± 4.72 46.74 ± 5.09

Female subgroups IVM WM

BAC 0.5 ± 0.02 g/l

Refraining-Control drink 55.62 ± 5.49 40.41 ± 4.05

Refraining Alcohol 17.52 ± 3.69*** 34.98 ± 5.07
BD-Control drink 40.51 ± 5.43+ 36.05 ± 3.26
BD-Alcohol 31.65 ± 5.79# 30.37 ± 4.04
Figure 1. Performance of the IVM task (mean ± SEM) in males with a BAC of
Experiment 2 0.33 ± 0.08 g/l. **P < 0.01 versus Control drink.
BAC 0.38 ± 0.08 g/l

Male subgroups IVM WM

Refraining-Control drink 40.75 ± 6.78 58.24 ± 5.75

Refraining Alcohol 34.05 ± 10.95 57.54 ± 8.9
BD-Control drink 44.73 ± 5.65 51.37 ± 4.99
BD-Alcohol 21.32 ± 7.44* 42.2 ± 7.17

Female subgroups IVM WM

Refraining-Control drink 55.62 ± 5.49 40.41 ± 4.05

Refraining Alcohol 18.05 ± 5.5*** 41.12 ± 7.58
BD-Control drink 40.51 ± 5.43 36.05 ± 3.26
BD-Alcohol 33.08 ± 10.94 35.33 ± 7.21

IVM, immediate visual memory; WM, working memory; BD, binge drink-
ing. ***P < 0.001 versus Refraining-Control drink in women of the same
experiment, #P < 0.05 versus Refraining Alcohol in women of the same
experiment, +P = 0.053 versus Refraining-Control drink in women of the Figure 2. Performance of the IVM task (mean ± SEM) in females with a BAC
same experiment, *P < 0.05 versus BD-Control drink in men of the same of 0.5 ± 0.02 g/l. ***P < 0.001 versus Refraining-Control drink; #P < 0.05 ver-
experiment. Data are presented as mean ± SEM. sus Refraining Alcohol.
614 Alcohol and Alcoholism, 2017, Vol. 52, No. 5

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Figure 3. Performance of the IVM task (mean ± SEM) in men and females with a BAC of 0.38 ± 0.08 g/l. ***P < 0.001 versus Refraining-Control drink in women;
*P < 0.05 versus BD-Control drink in men.

Pattern and Treatment on WM was not statistically significant

(F(1,74) = 0.242, ns).
In women, WM was not significantly different in subjects given
the control drink versus those receiving the alcohol Treatment
(F(1,88) = 1.651, ns), and the effect of Drinking Pattern was not
statistically significant (F(1,88) = 1.096, ns). No effect of the inter-
action between Treatment and Drinking Pattern on WM perform-
ance was detected (F(1,88) = 0.001, ns).

Experiment 2: Effects of a high dose of alcohol on

performance of memory tests in adolescent males
versus females (BAC: 0.38 ± 0.08 g/l) with a history
of BD alcohol or having refrained from alcohol use
Immediate visual memory Figure 4. Performance of the WM task (mean ± SEM) in males and females.
+++
Administration of the alcoholic drink led to lower IVM scores than P < 0.005 versus men.

administration of a control drink (F(1,126) = 14.139, P < 0.001).

However, there were no significant main effects of Drinking Pattern
(F(1,126) = 0.109, ns) or Gender (F(1,126) = 0.226, ns). The interac-
tions between Treatment and Drinking Pattern (F(1,126) = 0.436,
ns), Treatment and Gender (F(1,126) = 0.620, ns) and Drinking
Pattern and Gender (F(1,126) = 0.111, ns) were not significant.
However, the three-way interaction between Treatment, Drinking
Pattern and Gender (see Fig. 3) was found to be significant (F(1,126) =
4.93, P < 0.05). Pairwise comparisons of the interaction indicated that
women, but not men, with a history of refraining from drinking had
lower scores when given alcohol than when given the control drink
(F(1,32) = 19.073, P < 0.001). Among binge drinking subjects, men
but not women had lower scores when given alcohol than when given
the control drink (F(1,32) = 19.073, P < 0.001).
Working memory
Subjects receiving the alcohol Treatment were not significantly differ-
ent from controls with respect to WM performance (F(1,126) = 0.27,
ns), and there was no statistically significant effect of Drinking Pattern
on WM (F(1,126) = 3.916, ns). The factor Gender was significant
(F(1,126) = 11.82, P < 0.005), as men performed better than women
(see Fig. 4). The interactions between Treatment and Drinking Pattern
(F(1,126) = 0.36, ns), Treatment and Gender (F(1,126) = 0.389, ns)
and Drinking Pattern and Gender (F(1,126) = 0.578, ns) and
Treatment, Drinking Pattern and Gender (F(1,126) = 0.19, ns) were
not significant.
DISCUSSION
Alcohol consumption is highly prevalent during adolescence in
many countries, and an increase in BD has become apparent among
young people, especially women, over recent years (Hibell et al.,
2007; Chavez et al., 2011; OED, 2016). This pattern of consump-
tion (based on repeated alternations between acute intoxication and
withdrawal periods) is particularly neurotoxic, independently of the
global alcohol intake, with the cognitive consequences perhaps hav-
ing been underestimated (Maurage et al., 2012).
With this in mind, our first hypothesis was that the long-term
effects of repeated alcohol exposure during adolescence (such as
alcohol tolerance or damaged cognitive abilities) would be linked to
relationships between a history of BD and the magnitude of deficit
that occurs following an acute high dose of alcohol. Our results con-
firmed this hypothesis in the case of the IVM abilities of adolescent
Alcohol and Alcoholism, 2017, Vol. 52, No. 5
women with an average BAC of 0.5 ± 0.02 g/l. There was an inter-
action with IVM task performance, in which women refrainers given
alcohol performed worse than those given a control drink, while
alcohol or control drink administration produced no difference in
women binge drinkers. This interaction may be explained by two
separate processes. Firstly, women binge drinkers given the con-
trol drink did worse in the IVM task than refrainers given the con-
trol drink, indicating an association between BD and impaired
performance in this memory ability, even during the absence of
alcohol. Although this effect was only marginally significant, it
reinforces the findings of previous studies reporting links between
frequent alcohol use in adolescence and brain structural changes
or cognitive deficits (De Bellis et al., 2005; Guerri and Pascual,
2010; Squeglia et al., 2011; Alfonso-Loeches et al., 2013).
Secondly, female binge drinkers given alcohol scored better than
refrainers given alcohol. This effect suggests that tolerance reduces
the performance deficit in this task after drinking alcohol. This
phenomenon of cognitive tolerance is also reinforced by the fact
that the IVM performance of female binge drinkers receiving the
alcoholic drink did not differ from that of binge drinkers given the
control drink.
Although tolerance to alcohol is a well-known fact, few data are
available on the prevalence of tolerance in non-dependent adolescents
and young adults (Schuckit et al., 2008). Furthermore, there is con-
flicting evidence about the effects of tolerance to alcohol on memory.
It has been conjectured that previous failures to detect an effect of tol-
erance to alcohol on memory could reflect changes in neuropsycho-
logical functioning resulting from years of heavy drinking
(Poulos et al., 1981). Longitudinal results also show that the
effect of tolerance to alcohol is less likely to be developed on
cognitive skills than on fine motor skills in heavy drinkers
(Brumback et al., 2017). In fact, the development of tolerance in
young non-dependent drinkers could be obscured by additional
factors. Thus, maturation-related physiological changes that
occur in the mid-teens-to-early-20s might be mistaken for toler-
ance in that they contribute to a reduced effect of alcohol as the
individual grows older and the brain matures, becoming less
reactive to alcohol (Chung et al., 2001; Wells et al., 2006).
In males with a BAC of 0.33 ± 0.08 g/l, an overall main effect of
acute alcohol on IVM performance was observed so that those
receiving alcohol performed worse than those receiving the control
drink. There was evidence neither of neurotoxic effects of Drinking
Pattern nor the tolerance phenomenon in men.
In Experiment 2, females and males had a similar BAC of 0.38 ±
0.08 g/l and could be statistically compared, evaluating gender differ-
ences in order to contrast our second hypothesis. In the IVM task,
women developed cognitive tolerance to alcohol, unlike men. This
effect was less pronounced than in Experiment 1. We consider that
the development of tolerance in IVM depends on BAC, as when
BAC increases the effect of tolerance becomes more obvious, with
significant differences not only between female refrainers who
received alcohol versus refreshment, but also between female refrai-
ners versus binge drinkers receiving alcohol, when BAC was higher
(Experiment 1). It is possible that men with a BAC higher than that
of the subjects in the present study would display a cognitive toler-
ance effect of alcohol on IVM.
In the WM task, males and females with different or similar
BAC were not affected by alcohol consumption or BD pattern.
Other studies have reported that young binge drinkers exhibit
anomalies in neural activity involved in attentional/WM processes,
and suggest that this anomalous neural activity reflects underlying
615
dysfunctions in neurophysiological mechanisms, as well as the
recruitment of additional attentional/WM resources to enable said
binge drinkers to perform the task adequately (López-Caneda et al.,
2013). The effect of gender showed that men performed better than
women. Some evidence obtained in adult subjects suggests that visuo-
spatial functioning of the WM is superior in males than in females
(Rizk-Jackson et al., 2006). However, it should be mentioned that
few adult studies have examined sex differences in WM, and those
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have reported mixed results (Lejbak et al., 2011).
It has been found that individuals with low sensitivity to the
acute effects of alcohol show increased P3 event-related potential
reactivity to alcohol cues (Bartholow et al., 2007, 2010). This low
alcohol sensitivity is a risk factor for the development of AUDs.
Despite that men generally report lower sensitivity to alcohol than
women (e.g. Petit et al., 2013), the female adolescent drinkers in
our study showed cognitive tolerance and therefore may be more
likely than males to develop additional alcohol-related problems.
This is in accordance with the view that women are more suscep-
tible than men to the cognitive consequences of alcohol use
(Caldwell et al., 2005; Squeglia et al., 2011). Given the clinical
implications derived from varying sensitivity to alcohol (Schuckit
et al., 2008), we will include an alcohol sensitivity questionnaire in
our future research.
The limitations of this study are the aforementioned lack of an
alcohol sensitivity measure and the inherent limitation of the use of
self-reported data about alcohol use. Likewise, other variables, as
depression and impulsivity, could have interfered with the interpret-
ation of the results. It is also unclear whether the differences
observed between BD and refraining subjects were consequences of
the BD pattern or whether they were present before BD commenced,
in which case they might provide clues to the origins of BD. This is
relevant, as prolonged and heavy alcohol use might further weaken
already existing deficiencies (Peeters et al., 2015). Exploring this
issue is difficult in human studies with adolescent subjects under
legal age, but the available literature suggests that BD is associated
with neural abnormalities during adolescence (Squeglia et al., 2014).
In humans, structural brain changes resulting from problematic
drinking and leading to disrupted memory performance have been
reported (Bagga et al., 2014). Longitudinal studies that include the
time of onset of adolescent BD would be useful in establishing
the causes and effects of this pattern of alcohol use. Discovering the
causes and effects of individual differences in alcohol consumption
patterns is instrumental to designing programmes and policy to
reduce the impact of drinking in a highly vulnerable population
such as adolescent and young people.
In view of these results, and despite the aforementioned limita-
tions, our study suggests that (a) IVM is more sensitive than WM to
impairment by alcohol and (b) adolescent women are more vulner-
able to the neurotoxic effects of alcohol than men, because the cog-
nitive tolerance effect of alcohol on IVM develops in BD women but
not in BD men. The ‘telescoping effect’ is described as the phenom-
enon of women beginning to drink earlier and progressing more
rapidly from drinking onset to problem drinking compared to men
(Piazza et al., 1989; Johnson et al., 2005; Sugarman et al., 2009).
This effect may help to understand why adolescent women develop
cognitive tolerance before men.
ACKNOWLEDGEMENT
The authors wish to thank Mr Brian Normanly for his editorial assistance.
616
FUNDING
This work was supported by the ‘Generalitat Valenciana’ [PROMETEO/
2011/048; PROMETEO-II/2015/020] and ‘Ministerio de Economía y
Competitividad’ [PSI2013−44491-P], Spain.
CONFLICT OF INTEREST STATEMENT
None declared.
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