J Comp Physiol B (2005) 175: 533–541
DOI 10.1007/s00360-005-0007-1
R EV IE W
Frank Seebacher Æ Craig E. Franklin
Physiological mechanisms of thermoregulation in reptiles: a review
Received: 15 February 2005 / Revised: 29 April 2005 / Accepted: 20 May 2005 / Published online: 27 July 2005
Ó Springer-Verlag 2005
Abstract The thermal dependence of biochemical reac-
tion rates means that many animals regulate their body
temperature so that fluctuations in body temperature are
small compared to environmental temperature fluctua-
tions. Thermoregulation is a complex process that in-
volves sensing of the environment, and subsequent
processing of the environmental information. We sug-
gest that the physiological mechanisms that facilitate
thermoregulation transcend phylogenetic boundaries.
Reptiles are primarily used as model organisms for
ecological and evolutionary research and, unlike in
mammals, the physiological basis of many aspects in
thermoregulation remains obscure. Here, we review re-
cent research on regulation of body temperature, ther-
moreception, body temperature set-points, and
cardiovascular control of heating and cooling in reptiles.
The aim of this review is to place physiological ther-
moregulation of reptiles in a wider phylogenetic context.
Future research on reptilian thermoregulation should
focus on the pathways that connect peripheral sensing to
central processing which will ultimately lead to the
thermoregulatory response.
Keywords Body temperature Æ Evolution Æ
Thermoreception Æ Endothermy Æ Ectothermy Æ
Metabolism Æ Control Æ Heat Æ Cardiovascular
Abbreviations TRP: Transient receptor potential Æ NO:
Nitric oxide Æ NOS: Nitric oxide synthase Æ COX:
Communicated by I.D. Hume
F. Seebacher (&)
Integrative Physiology, School of Biological Sciences A08,
University of Sydney, Sydney, NSW 2006, Australia
E-mail: fseebach@bio.usyd.edu.au
Tel.: +61-2-93512779
Fax: +61-2-93514119
C. E. Franklin
School of Integrative Biology, The University of Queensland,
St. Lucia, QLD 4072, Australia
Cyclooxygenase enzyme Æ CPT:
8-Cyclopentyltheophylline
Introduction
The thermodynamic dependence of biochemical reaction
rates makes thermal physiology the most pervasive
component in the biology of animals. There are two
principle, but not mutually exclusive, trajectories along
which the thermal physiology of vertebrate animals has
evolved. On the one hand, there is a trend towards
regulating body temperature very precisely within nar-
row bounds regardless of environmental conditions
(DiBona 2003). On the other trajectory, physiological/
biochemical reaction rates have evolved to be plastic
within individuals and/or between populations and
species with the result that functional rates are main-
tained despite considerable variation in body tempera-
ture (Guderley and St. Pierre 2002; Johnston and
Temple 2002; Guderley 2004).
In this review, we focus on the regulation of body
temperature and the physiological mechanisms that
facilitate thermoregulation, rather than thermal plastic-
ity and temperature compensation of reaction rates. The
opportunity for thermoregulation is limited in thermally
homogenous environments, particularly in water where
the large convection coefficients rapidly equalise thermal
differentials between an animal and its environment.
Except for those animals that are very large or extremely
well-insulated, body temperature of aquatic organisms
tends to equal that of the water, and aquatic animals
compensate biochemically and physiologically for tem-
porally varying body temperatures and/or their distri-
bution is restricted to favourable climatic regions. On
land, daily regulation of body temperature is facilitated
by the heterogeneity of the thermal environment, and
relatively low heat transfer rates in air. Thermoregula-
tion is a complex process that must integrate sensing of
temporal and spatial variation in the thermal environ-
ment with behavioural and physiological responses that
534
will result in a narrow range of body temperatures rel-
ative to operative temperatures fluctuations (Seebacher
and Shine 2004).
The aim of this review is to summarise recent research
on physiological mechanisms of body temperature con-
trol, and to place reptiles within the broader framework
of vertebrate thermoregulation. Many traits of verte-
brates are evolutionarily conservative, and the future
direction in the field of reptilian thermal physiology can
be informed by the more intensive research efforts and
resultant detailed knowledge of mammalian thermo-
regulatory mechanisms. In the past 10–15 years, the
characterisation of molecular mechanisms involved in
thermoregulation, such as thermally sensitive proteins
and the various roles of nitric oxide, have been partic-
ularly significant. Hence, we will review some of the
more medically orientated literature on mammals along
with recent work on reptiles.
We will first provide a general summary of thermo-
regulatory mechanisms. Regulation of body temperature
presupposes that animals are capable of sensing their
environment, and of processing information. Hence, the
second and third section will review thermoreception
and set-points of body temperature regulation. In the
final section we will discuss cardiovascular mechanisms
of temperature control which are an essential compo-
nent of thermoregulation in both endotherms and ec-
totherms.
Regulation of body temperature
The principle physiological basis of body temperature
regulation in endotherms is the production of metabolic
heat in combination with thermal insulation (Kauffman
et al. 2001; Kvadesheim and Aarseth 2002; Seebacher
2003). Compared to ectotherms, increased metabolic
heat production in endotherms is in part owing to a
relative increase in metabolically active tissues—liver,
heart, and gastrointestinal systems (Fig. 1), to an in-
crease in cellular density of mitochondria, and to the
decoupling of metabolic pathways from ATP produc-
tion (Else and Hulbert 1981; Else and Hulbert 1985;
Brand et al. 1991). Specific decoupling mechanisms, such
as leaky membranes and uncoupling proteins (Brand et
al. 2004), lead to the electrochemical free-energy gener-
ated across the mitochondrial membrane to be dissi-
pated as heat rather than converted into chemical energy
by oxidative phosphorylation (Kadenbach 2003).
Uncoupling proteins are well-known from mammals
and birds (Nedergaard et al. 2001; Raimbault et al. 2001;
Brand et al. 2004; Kabat et al. 2004) but have as yet not
been reported from ectothermic reptiles.
The proportion of polyunsaturated fatty acids in the
composition of mitochondrial membranes is correlated
with the activity of membrane bound proteins. Mem-
brane composition may, therefore, be a principal
mechanism that regulates dissipation of the proton
gradient, and it may act as a metabolic pacemaker
Fig. 1 Comparisons between a mammal and a reptile. Sodium
pump concentrations (pmol mg protein 1) are not significantly
different between cows and crocodiles, but the molecular activities
(ATP/min) of the pumps are significantly greater in the cow (main
graph; data from Wu et al. 2004). The mass of the major organs
(ratio lizard:mouse shown) is significantly lower in reptiles than in
mammals (inset; data from Else and Hulbert 1981)
(Hulbert and Else 1999; Else and Hulbert 2003). Of
particular interest is docosahexaenoic acid (DHA) which
is an important modulator of membrane bound sodium
pump activity (Turner et al. 2003). Na+–K+ ATPase
concentrations are similar in microsomal membranes of
a crocodile and a cow, but enzyme activities were 4–5
fold greater in the cow compared to the crocodile
(Fig. 1). Delipidation of Na+–K+ ATPase and recon-
stitution with membranes across species (e.g. cow pro-
tein with crocodile membrane) provides direct evidence
that protein activity is determined by the membranes
(Wu et al. 2004). Additionally, endotherms have signif-
icantly greater concentrations of DHA and other poly-
unsaturated fatty acids compared to ectotherms (Brand
et al. 1994; Wu et al. 2004) so that there is a correlation
between protein activity and membrane fatty acid
composition.
Although internal heat production is negligible for
thermoregulation in ectothermic reptiles, metabolic heat
may be important for nest temperature regulation.
Developing alligator embryos may produce sufficient
metabolic heat to raise the temperature at the centre of
an egg cluster to 2–3°C above that of an open arrange-
ment of eggs (Ewert and Nelson 2003). Typically, how-
ever, reptiles thermoregulate behaviourally by exploiting
their thermal environment resulting in body tempera-
tures that fall within a narrow range for at least part of
the day (Hertz 1992; Hertz et al. 1993; Seebacher et al.
2003; Seebacher and Shine 2004). Basking in the sun is
one of the most typical thermal behaviours in reptiles
(Cowles and Bogert 1944; Seebacher 1999; Gvozdik
2002), although exposure to sun may have functions
other than thermoregulation. For example, the panther
chameleon’s (Furcifer pardalis) exposure to UV radia-
tion functions at least partly in regulating endogenous
 535

vitamin D3 production (Ferguson et al. 2003; Ferguson

et al. 2005). Photolytically produced vitamin D performs
a number of physiological functions, including regula-
tion of Ca2+ metabolism and cell signalling (Boyen et al.
2002).

Thermoreception

The efficacy of behavioural thermoregulation depends

on the capacity of animals to sense their thermal envi-
ronment. Sensing of environmental temperatures would
seem particularly important for animals that thermo-
regulate behaviourally because the targeted exploitation
of different thermal microhabitats requires contrasting
of environmental and internal temperatures (Cooper
2002). Specialised peripheral nerve endings that can re-
spond to both constant and variable temperatures are
known from several invertebrate and vertebrate taxa
(Cesare and McNaughton 1996; Caterina et al. 1997;
Viana et al. 2002; Brown 2003; Patapoutian et al. 2003;
Viswanath et al. 2003). In mammals, temperature may
be sensed by a family of transient receptor potential ion
channels (TRP) that are gated by specific temperatures
(Viswanath et al. 2003). These thermally activated TRPs
are located within the free nerve endings in the skin, but
are also found in the peripheral nervous system, brain,
heart and liver (Patapoutian et al. 2003). Six thermally
sensitive TRPs have been identified that each operate
over distinct temperature ranges (Fig. 2). Other trans-
ducers that have been implicated in thermosensing in
mammals include the two-pore domain K+ channels
(TREK-1; Caley et al. 2005).
A different sensing mechanism exists in sharks where
the electrosensitive ampullae of Lorenzini are capable of
sensing changes in environmental temperature (Brown
2003). Gel-filled canals connect pores at the surface of
sharks to the innervated ampullae situated subdermally.
The gel has the thermoelectric properties of a semicon-
ductor, thereby conveying thermal information from the
skin pores to the nerve endings in the ampullae (Brown
2003).
The pineal complex may act as a thermal sensor in
reptiles (Lutterschmidt et al. 1997), but specific neural
sensors associated with ion channels are not known from
reptiles. A possible exception are boid and crotaline
snakes that possess specific heat sensing organs (pit or-
gans; de Cock Buning 1983). Pit organs are innervated
by the trigeminal nerve in a sensory pathway that in-
volves protein kinase C as the signal transducer (Moon
et al. 2003), and are capable of detecting electromagnetic
radiation from near UV to infrared (Moiseenkova et al.
2003). The function of pit organs is thought to lie pri-
marily in prey detection and capture (de Cock Buning
1983; Shine and Sun 2002). The infrared receptors in the
pit organs of the snake Trimeresurus flavoviridis are
sensitive to temperature (Moon 2004), but their detec-
tion distance is very short (<0.005 m; Jones et al. 2001)
which would make it quite ineffective for predation
Fig. 2 Environmental sensing in vertebrates. a Heat stressed
rattlesnakes, Crotalus atrox, with intact pit organs (before) had
significantly greater success (proportion of all trials) in choosing a
thermally benign habitat than snakes with blocked pit organs
(blocked); when pit organs were unblocked (after), snakes regained
the ability to choose the benign habitat. A success rate of 0.5 would
be expected if choice was random. Data from Krochmal and
Bakken (2003). b Alligators and crocodiles possess dome pressure
sensors (blue arrow) on their head that are innervated by the
trigeminal nerve (Soares 2002; photo of Crocodylus johnstoni by
FS). c Mammals possess a family of transient receptor potential ion
channels (TRPV1–4, TRPV8, ANKTM1) each of which has a
different thermal sensitivity range. Data from Patapoutian et al.
(2003)
(Jones et al. 2001). Short detection distance could be
advantageous for thermoreception associated with
thermoregulation. Behavioural trials with the rattle-
snake, Crotalus atrox, indicate that pit organs are used
by the animals to detect thermally favourable micro-
habitats. When snakes in a maze were given the choice
of a thermally stressful (40°C) or a benign (30°C) envi-
ronment after being exposed initially to the stressful
environment, snakes with pit organs that were experi-
mentally blocked chose the benign refuge on signifi-
cantly fewer occasions than snakes with intact pit organs
(Krochmal and Bakken 2003; Fig. 2). This pattern of
preferentially choosing thermal refugia persisted across
12 pit viper species all of which possess facial pits, but
not in a true viper that lacks facial pits (Krochmal et al.
2004). Behavioural data therefore indicate that pit or-
gans are multifunctional, and that thermoregulation
536
rather than prey detection may even have been the
principle selection pressure leading to their evolution
(Krochmal et al. 2004).
Pit organs are the only known thermal sensors among
non-avian reptiles, although crocodilians possess exter-
nal pressure sensors, or dome pressure receptors (Soares
2002; Fig. 2). Dome pressure receptors are dome like
structures located on the head of crocodilians that are
covered externally by a considerably reduced keratin
layer, and which are innervated by the trigeminal nerve
(Soares 2002). The mechanisms of transduction of
pressure stimuli within the receptors are unknown—is it
possible that dome receptors also sense heat maybe via a
semiconductor mechanism?
Body temperature set-points
Body temperatures in thermoregulating reptiles may
vary temporally within individuals between day and
night and between seasons, and many species become
inactive when ‘‘preferred’’ body temperatures are unat-
tainable. Daily and seasonal fluctuations in behaviour
and physiological functions of reptiles—as well as of
other vertebrates—are regulated by the circadian sys-
tem. The circadian system acts as an endogenous oscil-
lator by integrating the hypothalamus, lateral eyes, the
pineal complex (Tosini et al. 2001), and, at least in
mammals, the retina (Sakamoto et al. 2004). Thermally
inspired behaviour in reptiles may be hormonally di-
rected, and melatonin in particular has been associated
with thermoregulation. Melatonin is produced by the
pineal gland and interacts with the thyroid gland, and it
may directly influence secretions of thyroid hormone
(Krotewicz and Lewinski 1994; Wright et al. 1996).
Melatonin may act as an intermediary between optical
signals, and behavioural and physiological responses
(Axelrod 1974). Levels of melatonin characteristic to
those produced in darkness have been observed to de-
crease the body temperature selected by a snake (Pit-
uophis melanoleucus; Lutterschmidt et al. 1997; Fig. 3).
Similar responses whereby selected body temperatures
are influenced by concentration of melatonin occur in
several species of reptile (e.g. Cothran and Hutchison
1979; Erskine and Hutchison 1981). Additionally, mel-
atonin levels also vary seasonally and may, therefore, act
to co-ordinate activity and thermoregulation with cli-
matic conditions on a daily and seasonal time scale
(Mendoça et al. 1995; Tosini and Menaker 1996).
Interestingly, however, intraperitoneal injections of
melatonin did not affect body temperature selection of a
nocturnal snake (Lamprophis fuliginosus) in a linear
thermal gradient compared to control treatments (Lut-
terschmidt et al. 2002; Fig. 3). Thermoregulatory
behaviour in toads also does not depend on melatonin
(Sievert and Poore 1995), and these findings may indi-
cate that there are fundamental differences in thermal
control centers between diurnal and nocturnal ecto-
therms.
Fig. 3 After treatment with melatonin, the diurnal bullnake
Pituophis melanoleucus selected significantly lower body tempera-
tures in a thermal gradient. In contrast, melatonin injection did not
alter the body temperature selection of the nocturnal African house
snake Lamprophis fuliginosus (Data from Lutterschmidt et al. 2002)
Selected body temperatures may be influenced by
environmentally induced changes in metabolic state. In
particular, low blood oxygen concentrations, either
brought about by intensive exercise or a hypoxic envi-
ronment can result in lower body temperatures (anapy-
rexia) in ectotherms and endotherms (Wagner and
Gleeson 1997; Steiner and Branco 2002; Petersen et al.
2003). Hypoxia increases adenosine release which may
interact with receptors on the hypothalamus to effect a
decrease in body temperature (Barros and Branco 1999).
For example, the selected body temperature of the lizard
Anolis sagrei is 34.8°C under normoxic conditions, but
exposure to hypoxic conditions in a thermal gradient
resulted in a significant 5°C drop in selected body tem-
peratures. Similarly, mean selected body temperatures
decreased by 4°C following exhaustive exercise. Intra-
peritoneal administration of the adenosine receptor
antagonist 8-cyclopentyltheophylline prevented or sub-
stantially reduced the hypoxia or exercise-induced drop
in mean selected body temperature (Petersen et al. 2003;
Fig. 4). However, administration of the adenosine
antagonist did not reduce selected body temperature
during normoxia (Petersen et al. 2003), and the reduc-
tion in body temperature during hypoxia may be a
mechanism to reduce O2 consumption.
Nitric oxide (NO), and the activity of nitric oxide
synthase (NOS), is instrumental in the brain of mam-
mals as a signalling molecule in the thermal response.
Inhibition of NOS by injection of inhibitors directly into
the lateral cerebral ventricle of rats caused a significant
hyperthermia that was sustained for several hours
(Mathai et al. 2004). Intravenous injection of the NOS
inhibitor L-NAME did not affect thermoregulation,
however, demonstrating that NO acts specifically in the
brain (Mathai et al. 2004). Interestingly, inhibiting
prostaglandin synthesis by administration of a non-ste-
roidal anti-inflammatory drug (indomethacin) before the
L-NAME treatment abolished the hyperthermic effect of
NOS inhibition (Mathai et al. 2004). The activity of

Fig. 4 Oxygen limitation induces anapyrexia in the lizard Anolis
sagrei. Body temperature selected in a thermal gradient was
significantly lower in hypoxic air (10% O2) compared to normoxia.
Similarly, selected body temperatures were decreased following
exhaustive exercise. Blockade of adenosine receptors with 8-
cyclopentyltheophylline (CPT), however, significantly reduced the
anapyrexia following hypoxia and exercise. Data from Petersen et
al. (2003)
cyclooxygenase enzyme (COX), which is responsible for
prostaglandin synthesis, may be controlled by NO
(Salvemini 1997), and the interaction between the
indomethacin and L-NAME treatments (Mathai et al.
2004) show that the NOS–NO–COX control axis is
important for thermoregulation in rats. The role of
prostaglandins in body temperature control and fever in
mammals is well-established (Feldberg and Saxena
1971), and direct injection of PGE2 into the hypotha-
lamic region of the rat brain causes an increase in the
thermogenic response (Madden and Morrison 2004).
Nitric oxide synthase is present in the brains of a turtle
(Brüning et al. 1994) and a lizard (Smeets et al. 1997),
but whether it functions in thermoregulation remains
unknown. Prostaglandins, on the other hand, alter the
thermoregulatory set-point in an amphibian (Bicego et
al. 2002) and a reptile (Bernheim and Kluger 1976) by
mediating a behavioural fever response following injec-
tion of an exogenous pyrogen. In the toad, Bufo pa-
racnemis, experimental lesions to the preoptic area of the
brain abolishes the characteristic pyrogen-induced fever
response (Bicego and Branco 2002), and it seems likely
that the prostaglandin-mediated reaction is situated in
the preoptic area. Additionally, both prostaglandins and
nitric oxide are important in cardiovascular responses
during thermoregulation in reptiles (see below; Seeb-
acher and Franklin 2003; Seebacher and Franklin
2004a).
Cardiovascular control of heat transfer
The efficacy of behavioural thermoregulation is deter-
mined to a large extent by cardiovascular changes
(Bartholomew and Tucker 1963; Grigg et al. 1979; Grigg
and Seebacher 1999; Seebacher and Grigg 2001; Dzia-
lowski and O’Connor 2001). It is advantageous for
reptiles that regulate body temperatures within a narrow
537
range relative to environmental (operative) temperature
fluctuations to control rates of heating and cooling while
moving in a thermally heterogeneous environment
(Seebacher 2000). Such control may be achieved by
altering cardiac output and the distribution of blood
flow in the body. Elevated cardiac output, achieved
primarily by increase in heart rate in reptiles, and
peripheral circulation will increase rates of transient heat
transfer between animals and their environment
(O’Connor 1999; Seebacher 2000; Seebacher and
Franklin 2004b). Hence, by increasing heart rates during
heating and decreasing heart rates during cooling rep-
tiles can exert control over heat exchange with the
environment (Fig. 5). This pattern, known as heart rate
hysteresis, has been described from all major lineages of
reptile (Bartholomew and Tucker 1963; Grigg et al.
1979). Interestingly, in crocodiles (Crocodylus porosus)
the magnitude of the hysteresis (i.e. difference in heart
rate between heating and cooling) depends on the mode
by which heat is transferred between the animal and its
environment. The heart rate differential between heating
and cooling is greatest during radiant heating, and heart
rate changes in proportion to the heat load experienced
at the animal surface (Franklin and Seebacher 2003;
Fig. 5). By analogy, similar cardiovascular changes are
the principle thermoregulatory mechanisms when
endothermic body temperatures are within the thermal
neutral zone (Romanovsky et al. 2002).
Preferential blood flow to the limbs during heating,
supported by increased cardiac output, may be one of
the mechanisms by which differential rates of heating
and cooling are achieved. Placing thermal insulation
around the limbs of Iguana iguana during heating and
cooling did not alter rates of heat exchange compared to
a control group, but a significant interaction between
heating/cooling and insulated/uninsulated limbs indi-
cates that limbs may be important in determining rates
of heating (Dzialowski and O’Connor 2004). Feeding
and digestion causes an increase in heart rate even be-
yond that resulting from heat. The additional cardiac
output in postprandial Varanus exanthematicus did not,
however, increase rates of heating and increased blood
flow after a meal appeared to be directed to the gut
without any thermoregulatory effect (Zaar et al. 2004).
Heart rate hysteresis consists of two phases, one a
very rapid (seconds) increase or decrease in heart rate in
response to application or removal of heat, respectively,
that occurs while body temperature remains stable. This
rapid response, which may represent a neural reflex arc,
is followed by a more gradual change in heart rate that is
proportional to changes in body temperature, and dur-
ing which heart rates during heating exceeds heart rate
during cooling at any given body temperature (Franklin
and Seebacher 2003). The rapid-response phase is at
least partly controlled by cholinergic and b-adrenergic
receptors, but autonomic blockade did not abolish the
hysteresis pattern in a lizard (Pogona barbata, Seebacher
and Franklin 2001). A second control system that may
act either alongside or instead of the autonomic nervous
538
Fig. 5 Reptiles control rates of heating and cooling by changing
heart rates (fH) and cardiac output. a fH is significantly higher
during heating compared to cooling (data from Seebacher and
Franklin 2003). b Modelled body temperatures for different heart
rates; increased heart rates lead to faster rates of heating and
decreased heart rates slow cooling. Body temperatures were model
according to methods in Seebacher (2000). c Changes in heart rate
(D fH) during heating and cooling (excluding the ‘‘reflex’’ period)
depend on the heat load received at the animal surface (curve:
Y=6.41*1.06x ; R2=0.74). Data from Franklin and Seebacher
(2003)
system are prostaglandins. Prostaglandin F2a and pros-
tacyclin cause a significant response in heart rate, and
inhibition of prostaglandins abolishes the characteristic
heart rate hysteresis response in the lizard Pogona vitti-
ceps (Seebacher and Franklin 2003). In contrast, inhi-
bition of cyclooxygenase enzyme did not affect heart rate
differential during heating and cooling in Crocodylus
porosus, and heart rate hysteresis persisted even with
double inhibition of nitric oxide synthase and cycloox-
ygenase enzyme (Seebacher and Franklin 2004a). Nitric
oxide did play a role during heating and cooling in C.
porosus, by buffering blood pressure against changes in
heart rate during cooling (Seebacher and Franklin
2004a).
The differences in the role of prostaglandins between
lineages (Squamata [P. vitticeps] and Archosauria [C.
porosus]) may indicate an evolutionary divergence of
control systems. The existence of heart rate hysteresis
during heating and cooling in a crustacean (Goudkamp
et al. 2004) indicates that this phenomenon may have
evolved alongside arterialisation of the vascular system
in organisms with principle regulatory mechanisms in
place. In the subsequent evolution of heart rate hysteresis
as a thermoregulatory trait different mechanisms that
control the cardiovascular system during thermoregula-
tion may have taken precedence in different lineages.
Conclusions and future directions
Thermoregulation is an integrated process involving
peripheral sensing, central processing, and co-ordination
of response functions that will affect body temperature.
Recent advances in thermal reception and temperature
control in non-reptilian vertebrates, particularly in
mammals, could inform the field of reptilian thermo-
regulation and guide future research efforts. The evolu-
tionary conservatism of many traits among vertebrates
suggests that there may exist a commonality of ther-
moregulatory mechanisms as well. Ectothermy is an
ancestral trait and comparisons between modern taxa
suggest that endotherms utilise many of the same prin-
ciple mechanisms of thermoregulation as ectotherms
(e.g. Else and Hulbert 1981).
Knowledge of thermoregulation in reptiles is con-
centrated on behavioural and ecological aspects and,
despite the recent advances reviewed here, some of the
essential mechanisms that underlie the whole animal
response remain poorly understood. There are several
traits known to be important in thermoregulation of
endotherms but not of ectothermic reptiles, e.g. uncou-
pling proteins, thermally sensitive proteins and neurons,
and the central control function of NO and COX. At
present, these differences probably reflect the disparate
research efforts on the respective groups rather than
evolutionary differences. Significant advances in under-
standing the evolution of thermoregulation will be made
when similarities and differences between different
groups of animals (endotherms–ectotherms, avian–non
avian reptiles, vertebrates–invertebrates, etc.) have been
experimentally established. Selection pressures act on
individual traits rather than on composite, whole animal
responses (Woods and Harrison 2002). To understand
the evolution of thermoregulation, it is essential to
understand the mechanisms that underlie the thermal
responses that are characteristic for each group.

Future research on reptilian thermoregulation should
focus on the pathways that connect peripheral sensing to
central processing which will ultimately lead to the ther-
moregulatory response. Sensing of the thermal environ-
ment is particularly important for behavioural
thermoregulation, and although the pineal complex and
melatonin provide a mechanism to process environmen-
tal conditions, it seems likely that there also exist other,
peripheral sensors. For example, restricted local heating
of a dorsal section in a crocodile and a lizard elicited a
distinct cardiovascular response (Morgareidge and White
1972; Grigg and Alchin 1976) that must have been inde-
pendent from direct stimulation of the pineal. Rather, we
speculate that peripheral thermal sensors are present in
reptiles, and these sensors may be similar to the inner-
vated thermal sensor proteins found in mammals and
Drosophila (Patapoutian et al. 2003). Central processing
of the peripheral thermal information may involve the
NOS–NO–COX axis that could integrate set-points and
cardiovascular control. It is of particular interest that the
cardiovascular response to heating and cooling in reptiles
is at least in part mediated by the integration between the
baroreflex and systemically acting NOS and COX en-
zymes (Altimiras et al. 1998; Seebacher and Franklin
2003; Seebacher and Franklin 2004a). A link between the
local and central functions of COX and NO may connect
environmental stimuli to the heart rate hysteresis that is
typical of reptilian thermoregulation.
Acknowledgments This work was supported by an Australian Re-
search Council Discovery grant to F.S. and C.E.F.
References
Altimiras J, Franklin CE, Axelsson M (1998) Relationship between
blood pressure and heart rate in the salt water crocodile Croc-
odylus porosus. J Exp Biol 201:2235–2242
Axelrod J (1974) The pineal gland: a neurochemical transducer.
Science 184:1341–1348
Barros RCH, Branco LGS (1999) Role of central adenosine in the
respiratory and thermoregulatory responses to hypoxia. Neu-
roreport 11:193–197
Bartholomew GA, Tucker VA (1963) Control of changes in body
temperature, metabolism, and circulation by the agamid lizard,
Amphibolurus barbatus. Physiol Zool 36:199–218
Bernheim HA, Kluger MJ (1976) Fever and antipyresis in the lizard
Dipsosaurus dorsalis. Am J Physiol 231:198–203
Bicego KC, Branco LGS (2002) Discrete electrolytic lesion of the
preoptic area prevents LPS-induced behavioral fever in toads. J
Exp Biol 205:3513–3518
Bicego KC, Steiner AA, Antunes-Rodrigues J, Branco LGS (2002)
Indomethacin impairs LPS-induced behavioral fever in toads. J
Appl Physiol 93:512–516
Boyen BD, Sylvia VL, Dean DD, Schwartz Z (2002) Membrane
mediated signalling mechanisms are used differentially by
metabolites of vitamin D3 in musculoskeletal cells. Steroids
67:421–427
Brand MD, Couture P, Else PL, Withers KW, Hulbert AJ (1991)
Evolution of energy metabolism. Biochem J 275:81–86
Brand MD, Couture P, Hulbert AJ (1994) Liposomes from mam-
malian liver mitochondria are more polyunsaturated and leak-
ier to protons than those from reptiles. Comp Biochem Physiol
108B:181–188
539
Brand MD, Affouttit C, Esteves TC, Green K, Lambert AJ, Miwa
S, Pakay JL, Parker N (2004) Mitochondrial superoxide: pro-
duction, biological effects, and activation of uncoupling pro-
teins. Free Rad Biol Med 37:755–767
Brown BR (2003) Sensing temperature without ion channels.
Nature 421:494–495
Brüning G, Wiese S, Mayer B (1994) Nitric oxide synthase in the
brain of the turtle Pseudemys scripta elegans. J Comp Neurol
348:183–206
Caterina MJ, Schumacher MA, Tominaga M, Rosen T, Levine JD,
Julius D (1997) The capsaicin receptor: a heat-activated ion
channel in the pain pathway. Nature 389:816–824
Cesare P, McNaughton P (1996) A novel heat-activated current in
nociceptive neurons and its sensitization by bradykinin. Proc
Natl Acad Sci USA 93:15435–15439
de Cock Buning T (1983) Thermal sensitivity as a specialization for
prey capture and feeding in snakes. Amer Zool 23:363–375
Cooper KE (2002) Molecular biology of thermoregulation. Some
historical perspectives on thermoregulation. J Appl Physiol
92:1717–1724
Cothran ML, Hutchison VH (1979) Effects of melatonin on ther-
mal selection by Crotaphytus collaris (Squamata: Iguanidae).
Comp Biochem Physiol A 63:461–466
Cowles RB, Bogert CM (1944) A preliminary study of the thermal
requirements of desert reptiles. Bull Am Mus Nat Hist 83:261–
296
DiBona GF (2003) Thermoregulation. Am J Physiol 284(2):R277–
R279
Dzialowski EM, O’Connor MP (2001) Physiological control of
warming and cooling during simulated shuttling and basking in
lizards. Physiol Biochem Zool 74:679–693
Dzialowski EM, O’Connor MP (2004) Importance of the limbs in
the physiological control of heat exchange in Iguana iguana and
Sceloporus undulatus. J Therm Biol 29:299–305
Else PL, Hulbert AJ (1981) Comparisons of the ‘‘mammal ma-
chine’’ and the ‘‘reptile machine’’: energy production. Am J
Physiol 240:R3–R9
Else PL, Hulbert AJ (1985) An allometric comparison of
the mitochondria of mammalian and reptilian tissues: the
implications for the evolution of endothermy. J Comp Physiol
156:3–11
Else PL, Hulbert AJ (2003) Membranes as metabolic pacemakers.
Clin Exp Parmacol Physiol 30:559–564
Erskine DJ, Hutchison VH (1981) Melatonin and behavioral
thermoregulation in the turtle, Terrapene carolina triunguis.
Physiol Behav 26:991–994
Ewert MA, Nelson CE (2003) Metabolic heating of embryos and
sex determination in the American alligator, alligator missis-
sippiensis. J Therm Biol 28:159–165
Feldberg W, Saxena PN (1971) Further studies on prostaglandin E
1 fever in cats. J Physiol 219:739–745
Ferguson GW, Gehrmann WH, Karsten KB, Hammack SH,
McRae M, Chen TC, Lung NP, Holick MF (2003) Do panther
chameleons bask to regulate endogenous vitamin D3 produc-
tion? Physiol Biochem Zool 76:52–59
Ferguson GW, Gehrmann WH, Karsten KB, Landwer AJ, Car-
man EN, Chen TC, Holick MF (2005) Ultraviolet exposure and
vitamin D synthesis in a sun-dwelling and a shade-dwelling
species of anolis: are there adaptations for lower ultraviolet B
and dietary vitamin D-3 availability in the shade? Physiol
Biochem Zool 78:193–200
Franklin CE, Seebacher F (2003) The effect of heat transfer mode
on heart rate responses and hysteresis during heating and
cooling in the estuarine crocodile Crocodylus porosus. J Exp
Biol 206:1143–1151
Goudkamp JE, Seebacher F, Ahern M, Franklin CE (2004)
Physiological thermoregulation in a crustacean? Heart rate
hysteresis in the freshwater crayfish Cherax destructor. Comp
Biochem Physiol A 138:399–403
Grigg GC, Alchin J (1976) The role of the cardiovascular system
in thermoregulation of Crocodylus johnstoni. Physiol Zool
49:24–36
540
Grigg GC, Drane CR, Courtice GP (1979) Time constants of
heating and cooling in the eastern water dragon, Physignathus
lesueruii, and some generalizations about heating and cooling in
reptiles. J Therm Biol 4:95–103
Grigg GC, Seebacher F (1999) Field test of a paradigm: hysteresis
of heart rate in thermoregulation by a free-ranging lizard
(Pogona barbata). Proc Roy Soc Lond B 266:1291–1297
Guderley H (2004) Metabolic responses to low temperature in fish
muscle. Biol Rev 79:409–427
Guderley H, St. Pierre J (2002) Going with the flow or life in the
fast lane: contrasting mitochondrial responses to thermal
change. J Exp Biol 205:2237–2249
Gvozdik L (2002) To heat or to save time? Thermoregulation in the
lizard Zootoca vivipara (Squamata: lacertidae) in different
thermal environments along an altitudinal gradient. Can J Zool
80:479–492
Hertz PE (1992) Temperature regulation in Puerto Rican
Anolis lizards: a field test using null hypotheses. Ecology
73:1405–1417
Hertz PE, Huey RB, Stevenson RD (1993) Evaluating temperature
regulation by field-active ectotherms: the fallacy of the inap-
propriate question. Am Nat 142:796–818
Hulbert AJ, Else PL (1999) Membranes as possible pacemakers of
metabolism. J Theor Biol 199:257–274
Johnston IA, Temple GK (2002) Thermal plasticity of skeletal
muscle phenotype in ectothermic vertebrates and its significance
for locomotory behaviour. J Exp Biol 205:2305–2322
Jones BS, Lynn WF, Stone MO (2001) Thermal modeling of snake
infrared reception: evidence for limited detection range. J Theor
Biol 209:201–211
Kabat AP, Rose RW, West AK (2004) Molecular identification of
uncoupling proteins 2 and 3 in a carnivorous marsupial, the
Tasmanian devil (Sarcophilus harrisii). Physiol Biochem Zool
77:109–115
Kadenbach B (2003) Intrinsic and extrinsic uncoupling of oxidative
phosphorylation. Biochim Biophys Acta 1604:77–94
Kauffman A, Cabrera A, Zucker I (2001) Energy intake and fur in
summer- and winter-acclimated Siberian hamsters (Phodopus
sungorus). Am J Physiol 281:R519–R527
Krochmal AR, Bakken GS (2003) Thermoregulation is the pits: use
of thermal radiation for retreat site selection by rattlesnakes. J
Exp Biol 206:2539–2545
Krochmal AR, Bakken GS, LaDuc TJ (2004) Heat in evolution’s
kitchen: evolutionary perspectives on the functions and origin
of the facial pit of pitvipers (Viperidae: Crotalinae). J Exp Biol
207:4231–4238
Krotewicz M, Lewinski A (1994) Thyroid hormone secretion in
male Wistar rats treated with melatonin and/or thyrotropin;
dependence of effects on the used doses. Neuroendocrin Lett
16:263–268
Kvadsheim PH, Aarseth JJ (2002) Thermal function of phocid seal
fur. Mar Mamm Sci 18:952–962
Lutterschmidt DI, Lutterschmidt WI, Hutchison VH (1997) Mel-
atonin and chlorpromazine: thermal selection and metabolic
rate in the bullsnake, Pituophis melanoleucus. Comp Biochem
Physiol C 118:271–277
Lutterschmidt DI, Lutterschmidt WI, Ford NB, Hutchison VH
(2002) Behavioral thermoregulation and the role of melatonin
in a nocturnal snake. Horm Behav 41:41–50
Madden CJ, Morrison SF (2004) Excitatory amino acid receptors
in the dorsomedial hypothalamus mediate prostaglandin-
evoked thermogenesis in brown adipose tissue. Am J Physiol
286:R320–R325
Mathai ML, Arnold I, Febbraio MA, McKinley MJ (2004) Central
blockade of nitric oxide induces hyperthermia that is prevented
by indomethacin in rats. J Therm Biol 29:401–405
Mendoça MT, Tousignant AJ, Crews D (1995) Seasonal changes
and annual variability in daily plasma melatonin in the red-
sided garter snake (Thamnophis sirtalis parietalis). Gen Comp
Endocrinol 100:226–237
Moiseenkova V, Bell B, Motamedi M, Wozniak E, Christensen B
(2003) Am J Physiol 284:R598–R606
Moon C (2004) An investigation of the effects of ruthenium red,
nitric oxide and endothelin-1 on infrared receptor activity in a
crotaline snake. Neuroscience 124:913–918
Moon C, Terashima S, Shin T (2003) Immunohistochemical
localization of the delta subspecies of protein kinase C in the
trigeminal sensory system of Trimeresurus flavoviridis, an
infrared sensitive snake. Neurosci Lett 338:233–236
Morgareidge KR, White FN (1972) Cutaneous vascular changes
during heating and cooling in the Galapagos marine iguana.
Nature 223:587–591
O’Connor MP (1999) Physiological and ecological implications of a
simple model of heating and cooling in reptiles. J Therm Biol
24:113–136
Patapoutian A, Peier AM, Story GM, Viswanath V (2003) Ther-
moTRP channels and beyond: mechanisms of temperature
sensation. Nature Rev Neurosci 4:529–539
Petersen AM, Gleeson TT, Scholnick DA (2003) The effect of
oxygen and adenosine on lizard thermoregulation. Physiol
Biochem Zool 76:339–347
Raimbault S, Dridi S, Denjean F, Lachuer J, Couplan E, Bouillaud
F, Bordas A, Duchamp C, Taouis M, Ricquier D (2001) An
uncoupling protein homologue putatively involved in faculta-
tive muscle thermogenesis in birds. Biochem J 353:441–444
Romanovsky AA, Ivanov AI, Shimansky YP (2002) Ambient
temperature for experiments in rats: a new method for
determining the zone of thermal neutrality. J Appl Physiol
92:2667–2679
Sakamoto K, Liu C, Tosini G (2004) Circadian rhythms in the
retina of rats with photoreceptor degeneration. J Neurochem
90:1019–1024
Salvemini D (1997) Regulation of cyclooxygenase enzymes by nitric
oxide. Cell Mol Life Sci 53:576–582
Seebacher F (1999) Behavioural postures and the rate of body
temperature change in wild freshwater crocodiles, Crocodylus
johnstoni. Physiol Biochem Zool 72:57–63
Seebacher F (2000) Heat transfer in a microvascular network: the
effect of heart rate on heating and cooling in reptiles (Pogona
barbata and Varanus varius). J Theor Biol 203:97–109
Seebacher F, Franklin CE (2001) Control of heart rate during
thermoregulation in the heliothermic lizard, Pogona barbata:
importance of cholinergic and adrenergic mechanisms. J Exp
Biol 204:4361–4366
Seebacher F, Franklin CE (2003) Prostaglandins are important in
thermoregulation of a lizard (Pogona vitticeps). Proc Roy Soc
Lond B (Suppl) 270:S50–S53
Seebacher F, Franklin CE (2004a) Integration of autonomic and
local mechanisms in regulating cardiovascular responses to
heating and cooling in a reptile (Crocodylus porosus). J Comp
Physiol B 174:577–585
Seebacher F, Franklin CE (2004b) Cardiovascular mechanisms
during thermoregulation in reptiles. Int Congr Ser 1275:242–
249
Seebacher F, Grigg GC (2001) Changes in heart rate are important
for thermoregulation in the varanid lizard, Varanus varius. J
Comp Physiol B 171:395–400
Seebacher F, Shine R (2004) Evaluating thermoregulation in rep-
tiles: the fallacy of the inappropriately applied method. Physiol
Biochem Zool 77:688–695
Seebacher F, Grigg GC, Beard LA (1999) Crocodiles as dinosaurs:
behavioural thermoregulation in very large ectotherms leads to
high and stable body temperatures. J Exp Biol 202:77–86
Seebacher F, Elsey RM, Trosclair PL III (2003) Body temperature
null-distributions in large reptiles: seasonal thermoregulation in
the American alligator (Alligator mississippiensis). Physiol
Biochem Zool 76:348–359
Shine R, Sun L (2002) Arboreal ambush site selection by pit-vipers
Gloydius shedaoensis. Anim Behav 63:565–576
Sievert LM, Poore JL (1995) Melatonin does not influence ther-
moregulatory behavior in Bufo americanus and Bufo marinus.
Copeia 1995:490–494
Smeets WJ, Alonso JR, Gonzalez A (1997) Distribution of
NADPH-diaphorase and nitric oxide synthase in relation to

catecholaminergic neuronal structures in the brain of the lizard
Gekko gecko. J Comp Neurol 377:121–141
Soares D (2002) An ancient sensory organ in crocodilians. Nature
417:241–242
Steiner AA, Branco LSG (2002) Hypoxia-induced anapyrexia:
implications and putative mediators. Annu Rev Physiol 64:263–
288
Tosini G, Menaker M (1996) The pineal complex and melatonin
affect the expression of the daily rhythm of behavioral thermo-
regulation in the green iguana. J Comp Physiol A 179:135–142
Tosini G, Bertolucci C, Foà A (2001) The circadian system of
reptiles: a multioscillatory and multiphotoreceptive system.
Physiol Behav 72:461–471
Turner N, Else PL, Hulbert AJ (2003) Docosahexaenoic acid
(DHA) content of membranes determines molecular activity of
the sodium pump: implications for disease and metabolism.
Naturwiss 90:521–523
Viana F, de la Pena E, Belmonte C (2002) Specificity of cold
thermotransduction is determined by differential ionic channel
expression. Nat Neurosci 5:254–260
Viswanath V, Story GM, Peier AM, Petrus MJ, Lee VM, Hwang
SW, Patapoutian A, Jegla T (2003) Opposite thermosensor in
fruitfly and mouse. Nature 423:822–823
541
Wagner EL, Gleeson TT (1997) Postexercise thermoregulatory
behavior and recovery from exercise in desert iguanas. Physiol
Behav 61:175–180
Woodbury CJ, Zwick M, Wang S, Lawson JJ, Caterina MJ, Kol-
tzenburg M, Albers KM, Koerber HR, Davis BM (2004)
Nociceptors lacking TRPV1 and TRPV2 have normal heat re-
sponses. J Neurosci 24:6410–6415
Woods HA, Harrison JF (2002) Interpreting rejections of the
beneficial acclimation hypothesis: when is physiological plas-
ticity adaptive? Evolution 56:1863–1866
Wright ML, Pikula A, Cykowski LJ, Kuliga K (1996) Effect of
melatonin on the anuran thyroid gland: follicle cell prolifera-
tion, morphometry, and subsequent thyroid hormone secretion
in vivo after melatonin treatment in vivo. Gen Comp Endo-
crinol 103:182–191
Wu BJ, Hulbert AJ, Storlien LH, Else PL (2004) Membrane lipids
and sodium pumps of cattle and crocodiles: an experimental
test of the membrane pacemaker theory of metabolism. Am J
Physiol 287:R633–R641
Zaar M, Larsen E, Wang T (2004) Hysteresis of heart rate and heat
exchange of fasting and postprandial savannah monitor lizards
(Varanus exanthematicus). Comp Biochem Physiol 137A:675–
682