INTEG.
AND
COMP. BIOL., 42:582–590 (2002)
Stress, Neuropeptides, and Feeding Behavior: A Comparative Perspective1
JAMES A. CARR2
Department of Biological Sciences, Texas Tech University, Box 4-3131, Lubbock, Texas 79409
SYNOPSIS.
Stress inhibits feeding behavior in all vertebrates. Data from mammals suggest an important
role for hypothalamic neuropeptides, in particular the melanocortins and corticotropin-releasing hormone
(CRH)-like peptides, in mediating stress-induced inhibition of feeding. The effects of CRH on food intake
are evolutionarily ancient, as this peptide inhibits feeding in fishes, birds, and mammals. The effects of
melanocortins on food intake have not been as extensively studied, but available evidence suggests that the
anorexic role of neuronal melanocortins has been conserved. Although there is evidence that CRH and the
melanocortins influence hypothalamic circuitry controlling food intake, these peptides may have a more
primitive role in modulating visuomotor pathways involved in the recognition and acquisition of food. Stress
rapidly reduces visually guided prey-catching behavior in toads, an effect that can be mimicked by administration of CRH, while corticosterone and isoproterenol are without effect. Melanocortins also reduce preyoriented turning movements and, in addition, facilitate the acquisition of habituation to a moving prey item.
The effects of these neuropeptides are rapid, occurring within 30 min after administration. Thus, changes
in neuroendocrine status during stress may dramatically influence the efficacy with which visual stimuli
release feeding behavior. By modulating visuomotor processing these neuropeptides may help animals make
appropriate behavioral decisions during stress.
INTRODUCTION
Most of us are reminded on a routine basis that
stress affects appetite and food intake. The effects of
stress on feeding are complex and depend upon a multitude of factors, not the least of which are the type,
intensity, and duration of the stressor. Nonetheless, in
every organism in which it has been studied, severe
psychological or physical stress reduces appetite and
food intake. To date, most research into this phenomenon has focused on the deleterious effects of stress
on appetite in mammals, with an emphasis on understanding the physiological basis of stress-related eating
disorders such as anorexia nervosa. Often overlooked
in this approach is the fact that the neuronal and endocrine mechanisms involved in human eating disorders are evolutionarily ancient and have been conserved as part of a process for rapidly redirecting behavior in response to a threat. In the acute phase of
this response, behaviors that are necessary for dealing
with an imminent threat (avoidance, escape) emerge
whereas feeding behavior is temporarily suspended.
Examples of this behavioral hierarchy appear in every
vertebrate group (Gilliam and Fraser, 1987; Abrahams
and Sutterlin, 1999; Carrascal and Polo, 1999; Lilliendahl, 2000; Whitham and Mathis, 2000; Ziemba et al.,
2000).
How do animals redirect behavior in response to a
threat? The antipredator behavior of anuran amphibians serves as an example. For a toad, the decision to
search for food in the presence of a predator (snake)
increases the likelihood that it will be captured and
eaten (Heinen, 1994). In contrast, if a toad stops mov-
ing and assumes a cryptic posture, it is less likely to
be contacted by a snake and subsequently eaten (Heinen, 1994). At the heart of this behavioral decision
making process are elementary visuomotor pathways
that have evolved to rapidly redirect behavior in response to a threat. These pathways are remarkably sensitive to the homeostatic and endocrine status of the
organism, in particular to hormones released during
stress.
The goal of this short review is twofold. The first
goal is to briefly review the effects of stress and stress
hormones on feeding in vertebrates. Although a number of hormones have been implicated in stress-induced feeding changes, this review will focus on the
role of neuropeptides. The second goal is to examine
the effects of stress and stress hormones on anuran
prey-catching as a means of illustrating the role of neuropeptides in redirecting behavior during stress.
A COMPARATIVE LOOK AT STRESS
BEHAVIOR
AND
FEEDING
A large volume of research indicates that stress affects feeding in mammals in a manner that depends
upon the duration and intensity of the stressor. Particularly intense painful (Antelman and Szechtman,
1975; Holland et al., 1977) or psychologically threatening (Shimizu et al., 1989) stressors inhibit feeding
(Table 1). In particular, physical restraint in rodents has
been used as a model for anorexia nervosa (Rybkin et
al., 1997), mainly because of its psychological nature.
In contrast, so-called mild stressors, such as a gentle
tail-pinch in rats, can cause spontaneous feeding (Morley et al., 1983). Endogenous opioids seem to play a
critical role in stress-induced eating (Morley et al.,
1983).
Stress-induced alterations in feeding are not restricted to mammals. Table 1 shows that a wide variety of
1 From the Symposium Stress—Is It More Than a Disease? A
Comparative Look at Stress and Adaptation presented at the Annual
Meeting of the Society for Integrative and Comparative Biology, 3–
7 January 2001, at Chicago, Illinois.
2 E-mail: [email protected]
582
STRESS
TABLE 1.
AND
FEEDING BEHAVIOR
583
Stressors affecting feeding behavior and food intake in fishes, amphibians, birds, and mammals.
Group/stressor
Effect on feeding
References
Fish
social subordination
simulated trawling
heavy metals
salt stress
carbaryl
Complete inhibition of feeding
Reversible reduction in feeding
Increase or decrease depending upon metal
70% reduction in food intake
Reduced feeding
Overli et al., 1998
Olla et al., 1997
McGeer et al., 2000
De Boeck et al., 2000
Arunachalam et al., 1980
Amphibians
Ether vapors, crowding
Reduced prey-catching behavior
Carr et al., (2002)
Birds
activated immune defense
caging density
LPS
Inclement weather
Emergency stage
Reduced feeding, reduced fecundity
Reduced food intake
Reduced food intake
Body weight loss
Increased foraging
Ilmonen et al., 2000
Goodling et al., 1984
Koh et al., 1996
Wingfield, 1984
Wingfield et al., 1998
Mammals
restraint
novel environment
strong tail pinch
cancer
LPS
surgery
mild tail pinch
Reduced food intake,
Reduced food intake,
Reduced food intake,
Reduced food intake,
Reduced food intake,
Reduced food intake,
Increase food intake
Rybkin et al., 1997
Morley et al., 1983
Antelman and Szechtman, 1975
Varma et al., 1999b
Plata-Salaman, 1999
Varma et al., 1999a
Antelman and Szechtman, 1975
weight
weight
weight
weight
weight
weight
loss
loss
loss
loss
loss
loss
LPS, lipopolysaccharide.
stressors affect feeding behavior in fishes, birds and
mammals, the groups that have been best studied. This
table is not meant to be exhaustive but rather to highlight the diversity and non-specific nature of the stressors that affect feeding. This is an important point to
keep in mind when considering the complexity of the
hypothalamic neuropeptidergic interconnections that
govern stress-induced changes in feeding.
STRESS-RELATED NEUROPEPTIDES AND FEEDING
BEHAVIOR
Several lines of evidence implicate hypothalamic
neuropeptides in the regulation of feeding. First, central administration of hypothalamic neuropeptides affects food intake and weight gain in mammalian and
nonmammalian vertebrates (see Inui, 1999; Ahima et
al., 2000; Lin et al., 2000 for recent reviews). Secondly, lesions of the hypothalamus have well-described effects on feeding behavior in humans (Celesia
et al., 1981) and lab mammals (Kalra et al., 1999).
Third, spontaneous genetic mutations or targeted gene
deletions that impair hypothalamic neuropeptide function have dramatic effects on feeding. Research into
the mechanism of leptin action has revealed that hypothalamic neuropeptides involved in coordinating the
neuroendocrine stress response, particularly the melanocortins and corticotropin-releasing hormone (CRH),
play a pivotal role in the normal maintenance of body
weight and energy metabolism. At the core of these
regulatory mechanisms lay complex interconnections
between discrete hypothalamic nuclei including the arcuate nucleus, the lateral hypothalamic area (LHA),
and the paraventricular nucleus (PVN). Although several hypothalamic peptides have been implicated in the
regulation of feeding, I will focus on two peptide families that have been linked to stress-induced alterations
in feeding.
Arcuate melanocortin neurons
Subsets of cells in the arcuate nucleus produce the
pro-hormone proopiomelanocortin (POMC). Posttranslational cleavage of POMC results in a number of
biologically active peptides including b-endorphin
(bE) and the melanocortin peptides, corticotropin
(ACTH) and alpha-melanocyte-stimulating hormone
(aMSH). Evidence supporting a physiological role of
melanocortins in feeding behavior came initially from
interest in the biological basis for coat color in agouti
mice. These mice ubiquitously over-express the agouti
protein, an endogenous melanocortin receptor antagonist (Lu et al., 1994). As a result, they develop a yellow coat. However, agouti mice also develop a form
of late-onset obesity similar to that occurring in mice
deficient in the melanocortin MC-4 receptor (Huszar
et al., 1997). MC-4 receptor antagonists block leptin
effects on weight gain (Seeley et al., 1997) while direct intracerebroventricular (i.c.v) administration of an
MC-4 agonist inhibits feeding in a wide variety of hyperphagic models (Fan et al., 1997). Leptin increases
POMC expression in arcuate neurons while leptin deficient mice express 50% less POMC in the arcuate
nucleus than wild-type mice (Schwartz et al., 1997).
A similar reduction in POMC expression is observed
in fasted mice (Schwartz et al., 1997). These findings,
with evidence that leptin receptors are expressed within arcuate POMC neurons (Cheung et al., 1997; Håkansson et al., 1998), point to a critical role for melanocortins in regulating feeding behavior. Melanocortins
584
JAMES A. CARR
TABLE 2. Stress-related hypothalamic neuropeptides and feeding
in vertebrates.
Neuropeptide
Group
Fish
Amphibians
Reptiles
Birds
Mammals
MSH
?
dec1
?
dec2
dec3
Opioid
4
inc
?
?
inc5
inc6
CRH*
dec7
dec8
?
dec9
dec10
* includes CRH-like peptides such as urocortin. Inc, increase; dec,
decrease.
1 Carpenter and Carr, 1996; Olsen et al., 1999.
2 Kawakami et al., 2000.
3 Vergoni et al., 2000.
4 De Pedro et al., 1995; De Pedro et al., 1996.
5 Maney and Wingfield, 1998; Deviche and Schepers, 1984.
6 Glass et al., 1999.
7 De Pedro et al., 1993.
8 Carr et al., 2002.
9 Furuse et al., 1997.
10 Spina et al., 1996; Bradbury et al., 2000.
inhibit feeding in amphibians and birds (Table 2), suggesting an evolutionarily ancient role as anorexigenic
neuropeptides. Although disruption of bE signaling
does not result in the dramatic effects on weight gain
observed with targeted disruption of melanocortin receptors (Huszar et al., 1997), direct i.c.v administration of this peptide increases feeding (McKay et al.,
1981; Table 2).
Paraventricular nucleus and CRH-like peptides
The PVN contains hypophysiotropic CRH neurons
that also play a role in the CNS control of feeding.
CRH potently inhibits feeding in every vertebrate
group so far examined (Table 2). A second CRH-like
peptide, urocortin, produced by neurons in the Edinger-Westphal nucleus (Vaughan et al., 1995), may also
be involved in feeding in mammals; urocortin is a
more potent inhibitor of feeding than CRH when administered i.c.v. (Spina et al., 1996). The receptor(s)
mediating these effects appear to have been evolutionarily conserved, as fish urotensin I inhibits feeding in
both fish (Bernier and Peter, 2001a) and mammals
(Negri et al., 1995). The role of CRH-like peptides
and their receptors in feeding is complex and beyond
the scope of this paper; the reader is referred to recent
discussions on the topic (Heinrichs and Richard, 1999;
Bradbury et al., 2000; Cone, 2000). Nonetheless, the
physiological importance of the PVN is clear, especially given the recent evidence that the PVN may be
the principal site of convergent orexic and anorexic
signals from the arcuate and LHA, thereby functioning
as sort of an ‘‘adipostat’’ (Cowley et al., 1999).
Hypothalamic neuropeptides mediate stress-induced
changes in feeding behavior
Given the involvement of melanocortins and CRH
in mediating leptin action, it is not surprising to see
that some of these same neuropeptides are involved in
stress-induced affects on feeding. Restraint-stress in-
duced anorexia in rats is partially-reduced after administration of the CRH-receptor antagonist a-helical
CRH (9–41) (Krahn et al., 1986) and is completely
inhibited by immunoneutralization of CRH (Shibasaki
et al., 1988). CRH is also involved in anorexia nervosa, as CSF CRH is elevated in patients with this disorder (Hotta et al., 1986). A role for melanocortins is
suggested by evidence that administration of the MC4
antagonist HS014 reduces stress-induced anorexia
(Vergoni et al., 1999a). The effects of CRH are not
mediated by the melanocortins, as HS014 does not
block CRH-induced anorexia (Vergoni et al., 1999b).
An interesting problem arises when one considers
that bE and aMSH are produced from the same prohormone (POMC) but have opposite effects on feeding. Nonetheless, feeding-related changes in arcuate
POMC expression generally support an anorexigenic
role for these neurons. Neurotoxin-induced transient
hyperphagia and weight gain are both associated with
decreased POMC expression and levels of aMSH in
the PVN, effects that can be reversed with administration of the non-selective MC-3/MC-4 agonist MT-II
(Dube et al., 2000). Obese Zucker rats have lower arcuate POMC gene expression and reduced aMSH content in the PVN compared to lean Zucker controls
(Kim et al., 2000). Interestingly, bE content in the
PVN is unchanged in obese Zucker rats, suggesting
differential secretion and/or metabolism of POMC
end-products in the PVN (Kim et al., 2000).
Stress and prey-catching in anuran amphibians
Although the neuropeptidergic control of feeding
has been studied in nonmammals, particularly in fishes
(Lin et al., 2000), little is known about the role of
neuropeptides in stress-induced inhibition of feeding
in nonmammals (Bernier and Peter, 2001b). We have
examined the role of stress-related neuropeptides in a
simple model of visually-guided feeding in toads.
Toads generally feed on small insects such as worms,
ants, crickets, and beetles. Movement and configurational aspects of these prey-stimuli are pre-programmed in the toad’s CNS. Presenting a toad with a
cardboard rectangle of the appropriate configuration
(long axis parallel to direction of movement 5 worm)
triggers the same series of ballistic movements (orienting → approaching → snapping) that a toad would
perform in response to real prey. Exposure to a noxious stimulus (ether vapors) or crowding inhibit preycatching (Carr et al., 2002). Adult toads respond to
noxious stimuli by releasing corticosterone (Olsen et
al., 1999), presumably due to CRH activation of the
pituitary-adrenal axis, as in mammals. Administration
of ovine CRH (oCRH), a form of the peptide that is
weakly sequestered by CRH binding proteins (Valverde et al., 2001), causes a similar reduction in preycatching behavior (Carr et al., 2002). Interestingly,
toads treated with oCRH developed a marked pupillary dilation within 30 min (Zozzaro and Carr, 2002),
an indication of sympathetic stimulation (Morris,
1976). This is not entirely unexpected, as CRH acts
STRESS
AND
FEEDING BEHAVIOR
on CNS receptors to activate the sympathetic nervous
system in mammals (Brown et al., 1982). The effects
of CRH on prey-catching probably do not involve
sympathetic stimulation, however, as administration of
isoproterenol at a dose sufficient to cause maximal pupillary dilation does not affect responsiveness to a
prey-item (Carr et al., 2002). The effects of oCRH are
apparently not mediated by adrenocorticosteroid secretion, as administration of a dose of corticosterone that
elevates blood levels of the steroid to those seen during
stress (Carpenter and Carr, 1996; Olsen et al., 1999)
has no effect on prey-catching behavior (Carr et al.,
2002).
Several lines of evidence suggest that melanocortins
may be involved in stress-induced reductions in prey
catching. Early work by Horn et al. (1979) demonstrated that ACTH facilitated acquisition and delayed
extinction of habituation to a prey-dummy. Work in
our lab confirmed the work of Horn et al. (1979) and
extended these findings by showing that aMSH and
ACTH 4–10 but not des-acetyl aMSH or (Nle4, DPhe7) a-MSH facilitated acquisition (Carpenter and
Carr, 1996). The effects of melanocortins on habituation to a prey-item are dose-dependent, are not mediated by adrenal corticosteroids, and are direction and
stimulus specific, suggesting that they are not due to
fatigue or some type of non-specific sedative effect
(Carpenter and Carr, 1996; Olsen et al., 1999). The
effects of aMSH on acquisition may be mediated by
CNS receptors, as radiolabeled aMSH is detected in
CSF within 30 min after dorsal lymph sac injection
(Olsen et al., 1999).
The ability of melanocortins to influence habituation
is intriguing, given the similarity between habituation
and aversive (or threatening) stimulus effects (Ingle,
1983) and the fact that both habituation and response
to a threat are driven by the pretectum (Ewert, 1980).
Melanocortins affect stress-related behaviors in mammals, such as grooming (von Frijtag et al., 1998), a
behavior characteristically elicited in response to a
threatening stimulus. Immunoneutralization of central
ACTH decreases novelty-induced grooming in rats
(Dunn et al., 1979).
Two major lines of evidence suggest an endogenous
role for neuronal melanocortins in regulating feeding
behavior in toads. First, melanocortin neurons innervate areas involved in visuomotor processing (Rana
ridibunda, Benyamina et al., 1986; Bufo cognatus,
Kim and Carr, 1997; Xenopus laevis, Tuinhof et al.,
1998; Spea multiplicata, Venkatesan and Carr, 2001).
A second line of evidence is work in our lab showing
that that brain aMSH is altered during and after exposure to a noxious stimulus (Olsen et al., 1999) or
confinement (Kim and Carr, 1997). In response to both
types of stressors there is a marked decrease in telencephalic aMSH content, suggesting increased release
of the peptide by ascending melanocortin projections.
STRESS
AND
585
FEEDING: ECOLOGICAL
PERSPECTIVES
AND
ETHOLOGICAL
What are the selective forces guiding the evolution
of hypothalamic circuits for inhibiting feeding during
stress? To answer this question it is necessary to understand the costs associated with feeding for animals
living in their natural environment. An increasing body
of literature supports the idea that animals weigh the
benefits of feeding with a number of costs, one of the
most important being risk of predation (Ziemba et al.,
2000). The long-term consequences of the tradeoff between foraging and predation risk have been best-studied in birds. In birds, maintenance of fat reserves is
required to sustain energy metabolism during periods
when the animal cannot eat. Most birds, however,
maintain fat stores well below the physiological maximum, presumably because increased fat stores (and
consequently increased body weight) increase the risk
of predation (Witter and Cuthill, 1993). Simply stated,
an obese bird can quickly become a dead bird if it is
unable to escape a predator. Increasing body mass can
hinder take-off and escape from a predator (reviewed
in Lilliendahl, 2000). In addition, maintenance of increased body mass requires that the animal spend more
time foraging, thereby exposing itself to potential
predators. Birds reduce food intake and lose weight
when exposed to real or simulated predators (Carrascal
and Polo, 1999; Lilliendahl, 2000).
Predation risk can guide the evolution of neuronal
pathways that allow the animal to rapidly redirect behavior in response to a threat, a phenomenon most
clearly seen in animals with an elementary behavioral
repertoire, such as frogs and toads. Toads respond to
a predator such as a snake with a series of pre-programmed behaviors that include an immediate cessation of movement and a crouching posture. Large
looming objects, sometimes even an otherwise optimal
prey-stimulus (see above) oriented vertically (long axis
perpendicular to movement direction 5 anti-worm),
can elicit the same avoidance posture observed in response to a snake (Ewert, 1980). If predator and prey
stimuli are presented simultaneously during the feeding season, avoidance/escape behavior overrides feeding (Ewert, 1997). A similar behavioral hierarchy exists in other vertebrates. Both wild-type and growthenhanced transgenic Atlantic salmon reduce foraging
in the presence of a predator (Abrahams and Sutterlin,
1999) while salamanders wait longer before attacking
prey when presented with chemical cues from a natural
predator (Whitham and Mathis, 2000). Tiger salamander larvae will reduce feeding to avoid being preyed
upon by conspecific cannibalistic salamanders (Crowley and Hopper, 1994). Smaller non-cannibalistic salamanders respond to conspecific cannibals as a threat,
and presumably forage less to decrease the likelihood
of being detected and eaten by the larger cannibal
forms (Ziemba et al., 2000). Captive greenfinches
(Carduelis chloris) stop foraging and lose body mass
586
JAMES A. CARR
in the presence of a perceived predator (Lilliendahl,
2000).
The neuroanatomical pathways underlying predator/
prey decision making have been well studied in anurans. Anatomical, electrophysiological, and behavioral/lesion studies support a retinal → tectum/pretectum
→ medullary → spinal cord pathway for responding
to prey (Fig. 1A). At least seven types of tectal neurons that respond to various aspects of prey-configuration and project to medullary motor control areas
have been identified (Ewert, 1997). Retino-recipient
neurons in the caudal thalamus/pretectum drive predator avoidance behavior, in part via an inhibitory interaction with the tectum (Fig. 1B). So-called ‘‘predator-detector’’ neurons in the pretectum (class TH3 and
TH4 according to Ewert, 1997) project to the ipsilateral tectum and inhibit tectal firing. Lesioning the pretectum eliminates avoidance behavior and prevents the
habituation that normally occurs when a non-rewarding prey-stimulus is presented repeatedly over time.
Over-driving the pretectal-tectal inhibitory pathway
completely eliminates prey-catching, a phenomenon illustrated by lesioning the ventral striatum (Finkenstädt,
1987). This brain area indirectly modulates tectal bugdetector cells by tonically inhibiting the pretectum
through fibers carried in the lateral forebrain bundle
(Ewert et al., 1999; Fig. 1B). Lesioning the striatum
‘‘releases’’ pretectal-tectal inhibitory neurons, and the
animals do not respond to prey (Finkenstädt, 1989;
Patton and Grobstein, 1998).
HOW DO NEUROPEPTIDES INFLUENCE WHAT THE
TOAD’S EYE TELLS THE TOAD’S BRAIN?
Recent anatomical studies support the concept that
hypothalamic neuropeptides target sensory and motor
circuits involved in simple decision making processes,
such as predator/prey recognition. In amphibians and
reptiles, melanocortins innervate basal forebrain structures involved in subcortical visuomotor processing,
specifically the basal ganglia (Khachaturian et al.,
1984; Benyamina et al., 1986; Kim and Carr, 1997;
Tuinhof et al., 1998; Venkatesan and Carr, 2001; Fig.
1C). In toads, the basal ganglia are innervated by
POMC neurons (Kim and Carr, 1997; Venkatesan and
Carr, 2001). The striatum (and to a lesser degree the
nucleus accumbens) supply both direct and indirect innervation to the optic tectum (Wilczynski and Northcutt, 1983; Marin et al., 1997, 1998). By innervating
the basal ganglia, melanocortin neurons may gain access to multiple modes of tectal regulation.
Both CRH- and sauvagine-immunoreactive neurons
have been identified in the nucleus of the medial longitudinal fasciculus (nMLF) in the mesencephalic tegmentum of anurans. Neurons in the nMLF drive spinal
motor and interneurons in fish (Bosch et al., 1995;
Uematsu and Todo, 1997) and may participate in mediating tecto-spinal information flow during prey-orienting behaviors (Kostyk and Grobstein, 1987; Masino
and Grobstein, 1989). Whether CRH- or sauvagine
neurons in the nMLF participate in stress-induced in-
FIG. 1. Schematic sagittal section depicting the relationship between POMC neurons and visuomotor pathways in the brain of Bufo.
A. An overly simplified scheme of brain areas involved in preycatching and predator avoidance. Retino-recipient neurons in the
thalamus/pretectum (TH) respond to visual stimuli resembling a
predator while neurons in the optic tectum (OT) are programmed to
respond to prey stimuli. Prey detector cells innervate premotor circuits (PMS). Based on Ewert (1980) and Ewert (1997). B. The basal
ganglia (BG, nucleus accumbens, ventral and dorsal striatum) regulate tectal function via a direct and two indirect pathways; a thalamic/pretectal-tectal inhibitory pathway and a tegmental-tectal pathway. Basal ganglia-thalamic/pretectal inhibitory pathways originate
in the caudal ventral striatum based on lesion and electrical stimulation and recording studies (reviewed in Ewert et al., 1999). The
anatomy of the BG-tectal, BG-thalamic/pretectal-tectal, and BG-tegmental-tectal pathways are based on Wilczynski and Northcutt,
1977, 1983; Marin et al., 1997, 1998. Heavy dashed lines indicate
pathways that have been identified by tract tracing but have an undetermined role in modulating prey-catching. C. Infundibular POMC
neurons contribute to a major ascending projection innervating the
BG. Minor POMC projections innervate the OT. Light dashed lines
represent POMC neuronal pathways supported by immunocytochemistry but not confirmed by tract tracing. Immunocytochemcial
identification of pathways based on Kim and Carr (1997, Bufo cognatus), Venkatesan and Carr (2001, Spea multiplicata), Tuinhof et
al. (1998, Xenopus laevis), and Benyamina et al. (1986, Rana ridibunda). Tuinhof et al. (1998) have reported POMC neurons in the
striatum of X. laevis. Ad/Av, anterodorsal tegmental nucleus; anteroventral tegmental nucleus.
hibition of prey-catching remains to be seen, but deserves consideration given the well-documented effects of CRH on locomotor activity in fishes (Clements
and Schreck, 2001), amphibians (Moore et al., 1984;
STRESS
AND
FEEDING BEHAVIOR
Lowry et al., 1990) and mammals (Dunn and Berridge, 1990). In newts, CRH alters the discharge patterns of medullary neurons involved in locomotor behaviors (Lowry et al., 1996).
One could easily argue that stress-related neuropeptides affect feeding motivation simply by elevating
blood glucose titers. Elevated blood glucose rapidly
(within 15 min) shuts down feeding motivation in
toads (Laming and Cairns, 1998). However, this is not
a likely mechanism for melanocortin action as the effects of ACTH on habituation are stimulus and direction specific (Horn and Horn, 1982; Carpenter and
Carr, 1996). CRH has a slight but rapid hyperglycemic
effect in rats that is mediated via sympathetic stimulation (Brown et al., 1982). However, isoproterenol has
no effect on prey-catching (Carr et al., 2002). Whether
CRH effects blood glucose within the 30 min time
frame in which we see affects remains to be seen.
THE ADAPTIVE SIGNIFICANCE OF REDIRECTING
BEHAVIOR DURING STRESS
Is stress-induced inhibition of feeding adaptive?
Studies on the antipredator behavior of toads can provide insight into this question. According to Endler
(1991), organisms evolve antipredator behaviors in
concert with the major sensory mode(s) used by predators. Garter snakes are more likely to use visual over
olfactory cues when hunting toads (Heinen, 1995). In
turn, toads respond to a visual image of a snake by
reducing their movement and crouching low to the
ground, this latter behavior being identical to the
avoidance behavior generated by electrical stimulation
of the pretectum (Ewert, 1980). Unfed toads are more
likely to remain active in the presence of a predator
and subsequently more likely to be caught (Heinen,
1994). These studies suggest that the degree of satiety
can directly impact a toads survival in the presence of
a predator, which raises the speculative (and presently
untested) question: Are melanocortins and CRH satiety
and/or antipredator peptides? It is not unreasonable to
imagine that the satiety effects of these peptides are
just one component of a suite of defensive responses
engaged in a threatening situation.
CONCLUSIONS
Exposure to severe physical or psychologically
threatening stressors inhibits feeding in all vertebrates.
In mammals, hypothalamic neuropeptides such as
CRH and the melanocortins play a critical role in
stress-induced changes in feeding. Although there
have been remarkable advances in identifying intrahypothalamic pathways involved in stress-induced
feeding disorders (Cowley et al., 1999; Bell et al.,
2000), precisely how this information is parceled out
of the hypothalamus to brain areas involved in feeding
motivation is poorly understood. Research on anurans
suggests that stress-related neuropeptides interact with
elementary visuomotor pathways to inhibit visuallyguided feeding behavior. These pathways are directly
affected by motivational state (Laming and Cairns,
587
1998) and ensure that appropriate motor patterns are
rapidly engaged in response to changes in the animal’s
visual environment, such as the presence of a predator.
Pretectal-tectal inhibitory pathways ensure a rapid suspension of feeding and emergence of appropriate
avoidance behaviors. Pretectal-tectal inhibitory neurons are influenced, in turn, by inhibitory neurons in
the striatum, a target for melanocortin innervation in
nonmammalian vertebrates. Whether melanocortins
and CRH act to reduce feeding motivation or to engage antipredator behaviors is a major question for future research. At least some of the effects of CRH on
feeding may be independent of stress-induced escape
and fear-related behaviors, as peripheral administration
of urocortin reduces the rate of gastric emptying in lab
rodents (Asakawa et al., 1999; Wang et al., 2001).
Although the adaptive significance of reducing feeding behavior in response to a predator has been demonstrated experimentally, a major question that remains is why do animals respond in virtually the same
way to such a wide variety of non-specific threats (Table 1)? The answer probably lies in understanding how
afferent sensory information is directed to hypothalamic neuropeptidergic areas involved in feeding. The
interactions between hypothalamic neuropeptides and
visuomotor processing in the toad provides a simple
model for dissecting out how neuropeptides influence
behavioral decision making during stress.
ACKNOWLEDGMENTS
The studies reported here were supported in part by
funds from the Texas Tech University Research Enhancement Fund, a Howard Hughes Medical Institute
grant through the Undergraduate Biological Sciences
Education Program to TTU, and the NIH (MH53065).
The symposium was made possible by funding from
the NIMH (R13 MH62670), NSF (IBN 0100532), the
Center for Biomedical Research Excellence (CoBRE,
CHS) at the University of South Dakota on Neural
Mechanisms of Adaptive Behavior, South Dakota
EPSCoR, and the USD Office of Research.
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