Brain Reward Systems for Food Incentives and Hedonics in Normal Appetite and Eating Disorders

26 Pages·2006·5.72 MB·English

In Progress in Brain Research: Appetite and Body Weight. T.C. Kirkham &
S.J. Cooper (Eds.), Academic Press, pp. 191-216, 2007.
C H A P T E R
8
Brain Reward Systems for Food
Incentives and Hedonics
in Normal Appetite and
Eating Disorders
KENT C. BERRIDGE
I.Introduction
II.Possible Roles of Brain Reward Systems in Eating Disorders
A. Reward Dysfunction as Cause
B. Passively Distorted Reward Function as Consequence
C. Normal Resilience in Brain Reward
III.Understanding Brain Reward Systems for Food “Liking” and “Wanting”
A. Measuring Pleasure
B. Brain Systems for Food Pleasure
C. Pleasure Brain Hierarchy
D. Forebrain Limbic Hedonic Hot Spot in Nucleus Accumbens
E. Ventral Pallidum: “Liking” and “Wanting” Pivot Point for Limbic Food Reward Circuits
IV.“Wanting” without “Liking”
A. What Is “Wanting”?
B. Addiction and Incentive Sensitization
C. Is There a Neural Sensitization Role in Food Addictions?
D. Cognitive Goals and Ordinary Wanting
V.ABrief History of Appetite: Food Incentives, Not Hunger Drives
A. Separating Reward and Drive Reduction
VI.Connecting Brain Reward and Regulatory Systems
VII.Conclusion
Acknowledgments
References
What brain reward systems mediate disorders? This chapter identifies
motivational “wanting” and hedonic recent discoveries in hedonic “liking”
“liking” for food rewards? And what mechanisms, such as the location of opioid
roles might these systems play in eating hedonic hotspots in nucleus accumbens
191
192 8. BRAIN REWARD SYSTEMS FOR FOOD INCENTIVES AND HEDONICS IN NORMAL APPETITE
and ventral pallidum that paint a pleasure A. Reward Dysfunction as Cause
gloss onto sweet sensation. It also considers
First, it is possible that some aspects of
other incentive motivation systems that
brain reward function may go wrong and
mediate only a nonhedonic “wanting”
actually cause an eating disorder. Foods
component of reward, such as nearby
might become hedonically “liked” too
limbic opioid “wanting” zones, mesolimbic
much or too little via reward dysfunction.
dopamine contributions to incentive
Or incentive salience “wanting” to eat
salience, and other components of brain
mightdetachfromnormalcloseassociation
limbic systems, and discusses potential
with hedonic “liking,” leading to changes
roles in eating disorders.
inmotivatedfoodconsumptionthatareno
longer hedonically driven. Or yet again,
I. INTRODUCTION suppression of positive hedonic reward
systems or activation of dysphoric stress
systems might prompt persistent attempts
Obesity, bulimia, anorexia, and related
to self-medicate by eating palatable food.
eating disorders have risen in recent
All of these possibilities have been sug-
decades, leading to increasing concern. Can
gestedatonetimeoranother.Eachofthem
improved knowledge about brain reward
deserves consideration because different
systems guide us in thinking about eating
answersmightapplytodifferentdisorders.
disorders and normal eating?
First it is important to recognize that
brain reward systems are active partici- B. Passively Distorted Reward Function
pants, not just passive conduits, in the act as Consequence
of eating. Sweetness and other food tastes
are merely sensation, and their pleasure As a second category of possibilities,
arises within the brain. Hedonic brain brain reward systems might remain intrin-
systems must actively paint the pleasure sicallynormalandhavenoessentialpathol-
onto sensation to generate a “liking” ogy in eating disorders, but still become
reaction—as a sort of “pleasure gloss.” What distortedinfunctionasapassivesecondary
brain systems paint a pleasure gloss onto consequence of disordered intake. In that
sensation? And what brain systems convert case, brain systems of “liking” and
pleasure into a desire to eat? Answers to “wanting” might well attempt to function
these questions requires combining infor- normally. The abnormal feedback from
mation from neuroimaging experiments physiological signals that are altered by
and studies of eating in humans and infor- binges of eating or by periods of anorexia
mation from brain manipulation and phar- mightinducerewarddysfunctionasacon-
macological experiments that ethically can sequence of the behavioral disorder that
be done only in animals. arose from other causes. This would
provideapotentialredherringtoneurosci-
entistssearchingforcausesofeatingdisor-
II. POSSIBLE ROLES OF ders, because brain abnormalities might
BRAIN REWARD SYSTEMS IN appear as neural markers for a particular
EATINGDISORDERS disorder, but be mistaken as causes when
theywereactuallyconsequences.However,
To begin with, we can sketch several itmightstillprovideawindowofopportu-
alternative possibilities for how brain nity for medication treatments that aim
reward systems might function in any par- tocorrecteatingbehaviorinpartbymodu-
ticular eating disorder. Let us set out some lating reward function back to a normal
alternativestoframetheissue. range.
III. UNDERSTANDING BRAIN REWARD SYSTEMS FOR FOOD “LIKING” AND “WANTING” 193
C. Normal Resilience in Brain Reward
underlying factors are altering eating, even
though it will not reverse those causal
Third, it is possible that most aspects of
factors.
brain reward systems will function even
Or instead should treatment be focused
more normally than suggested by the pas-
entirely on separate brain or peripheral
sively distorted consequence model above.
targets that are unrelated to food reward?
Many compensatory changes can take place
That might be the best choice if brain
in response to physiological alterations, to
reward systems simply remain normal in all
oppose them via homeostatic or negative
cases of eating disorders, and thus perhaps
feedback corrections. The final consequence
essentially irrelevant to the expression of
of those compensations might restore nor-
pathological eating behavior.
mality to brain reward functions. In such
Placing these alternatives side by side
cases, the causes of eating disorder might
helps illustrate that there are therapeutic
then be found to lie completely outside
implications that would follow from a
brain reward functions. Indeed, brain
better understanding of brain reward
reward functions would persist largely nor- systems. Only if we know how food reward
mally, and may even serve as aids to even- is processed normally in the brain will we
tually help spontaneously normalize eating be able to recognize pathology in brain
behavior even without treatment. reward function. And only if we can recog-
The answer to which of these alternative nize reward pathology when it occurs will
possibilities is best may well vary from case we be able to judge which of the possibili-
to case. Different eating disorders may ties above best applies to a particular eating
require different answers. Perhaps even dif- disorder.
ferent individuals with the “same” disorder
will involve different answers, at least if
there are distinct subtypes within the major III. UNDERSTANDING BRAIN
types of eating disorder. REWARD SYSTEMS FOR FOOD
It is important to strive toward discover- “LIKING” AND “WANTING”
ing which answers are most correct for par-
ticular disorders or subtypes, because those This section turns to some issues
answers carry implications for what treat- involved in measuring and understanding
ment strategy might be best. For example, components of brain reward function
should one try to restore normal eating by (Berridge and Robinson, 2003; Everitt and
reversing brain reward dysfunction via Robbins, 2005). At the heart of reward is
medications to correct the underlying hedonic impact or pleasure, and so it
problem? That would be appropriate if is fitting to begin with the practical pro-
reward dysfunction is the underlying blem of measuring pleasure “liking” for
cause. food rewards in affective neuroscience
Or should one use drugs instead only studies.
as compensating medications, not cures?
Such a medication might aim to boost
A. Measuring Pleasure
aspects of brain reward function and so
correct eating, even though it may not Fortunately for psychologists and
address the original underlying cause? For neuroscientists, pleasure is not just a meta-
example, just as aspirin often helps treat physical will-o’-the-wisp. Pleasure is a psy-
pain, even though the original cause of pain chological process with neural reality, and
was never a deficit in endogenous aspirin, has objective markers in brain and behav-
so a medication that altered reward systems ior. These objective aspects give a tremen-
might still help to oppose whatever original dously useful handle to neuroscientists
194 8. BRAIN REWARD SYSTEMS FOR FOOD INCENTIVES AND HEDONICS IN NORMAL APPETITE
and psychologists in their efforts to gain a B. Brain Systems for Food Pleasure
scientific purchase on pleasure.
To identify the brain mechanisms that What brain systems paint a pleasure
generate pleasure we must be able to iden- gloss onto mere sensation? Many brain sites
tify when pleasure “liking” occurs or are activated in humans by food pleasures:
changes in magnitude. A useful “liking” Cortical sites in the front of the brain impli-
reaction to measure taste pleasure is the cated in the regulation of emotion, such as
affective facial expression elicited by the orbitofrontal cortex and anterior cingulate
hedonic impact of sweet tastes in newborn cortex, gustatory-visceral-emotion-related
human infants. Fortunately for pleasure zones of cortex such as insular cortex; sub-
causation studies, many animals display cortical forebrain limbic structures such as
“liking–disliking” reactions elicited by amygdala, nucleus accumbens, and ventral
sweet/bitter tastes that are similar and pallidum; mesolimbic dopamine projec-
homologous to affective facial expressions tions and even deep brainstem sites (Berns
to the same tastes displayed by human et al., 2001; Cardinal et al., 2002; Everitt
infants (Grill and Norgren, 1978b; Steiner, and Robbins, 2005; Kringelbach, 2004;
1973; Steiner et al., 2001). These affective Kringelbach et al., 2004; Levine et al., 2003;
expressions seem to have developed from O’Doherty et al., 2002; Pelchat et al.,
the same evolutionary source in humans, 2004; Rolls, 2005; Schultz, 2006; Small
orangutans, chimpanzees, monkeys, and et al., 2001; Volkow et al., 2002; Wang et al.,
even rats and mice (Berridge, 2000; Steiner 2004a). All of these code pleasurable foods,
et al., 2001). Sweet tastes elicit positive facial in the sense of sometimesactivating during
“liking” expressions (tongue protrusions,
the experience of seeing, smelling, tasting,
etc.), whereas bitter tastes instead elicit
or eating palatable foods.
facial “disliking” expressions (gapes, etc.).
But let us also ask: Which of these many
A particular set of taste “liking–dislik-
brain structures actually cause the pleasure
ing” reactions are remarkably similar across
of foods? Do all generate pleasure “liking”
species, and even their apparent differences
or only some? Some activations might
often reflect a deeper shared identity, such
reflect causes of pleasure, whereas other
as identical allometric timing laws for
activations might reflect consequences of
expression duration that are scaled to the
pleasure that was caused elsewhere. How
size of the species. For example, human or
can causation be identified? Typically only
gorilla tongue protrusions to sweetness or
by results of brain manipulation studies: a
gapes to bitterness may appear languidly
manipulation of a particular brain system
slow, whereas the same reactions by rats or
will reveal pleasure causation if it produces
mice seem blinkingly fast, yet, they are
an increase or decrease in “liking” reactions
actually the “same” reactions durations in
to food pleasure.
what is called an allometric sense; that is,
Recent years have seen progress in
each species is timed proportionally to their
identifying brain systems responsible for
evolved sizes and that timing is pro-
generating the pleasure gloss that makes
grammed deep in their brains. Such shared
palatable foods “liked” (Berridge, 2003;
universals further underline the common
Cardinal et al., 2002; Cooper, 2005; Higgs
brain origins of these “liking” and “dislik-
et al., 2003; Kelley et al., 2005a; Levine and
ing” reactions in rats and humans. That sets
Billington, 2004; Rolls, 2005; Wise, 2004;
the stage for animal affective neuroscience
Yeomans and Gray, 2002). What has
studies to use these affective expressions to
emerged most recently is a connected
identify brain mechanisms that generate
network of forebrain sites that use opioid
hedonic impact.
neurotransmission to increase taste “liking”
III. UNDERSTANDING BRAIN REWARD SYSTEMS FOR FOOD “LIKING” AND “WANTING” 195
and “wanting” together to enhance food in the brainstem. Normal “liking” reactions
reward. are not brainstem reflexes in a whole-
Pleasure “liking” appears to be gener- brained individual. This becomes obvious
ated by a distributed network of brain when we consider a related example: anen-
islands scattered across sites like an archi- cephalic infants cry and vocalize and even
pelago that trails throughout the limbic a decerebrate rat squeaks and emits distress
forebrain and brainstem (Berridge, 2003; cries if its tail gets pinched. But no one
Kelley et al., 2005a; Levine and Billington, would suggest the vocal ability of anen-
2004; Peciña and Berridge, 2005; Smith and cephalic infants to cry and decerebrate rats
Berridge, 2005). These sites include nucleus to squeak means that normal human speech
accumbens, ventral pallidum, and possibly is merely a brainstem reflex. Obviously
amygdala and even limbic cortical sites, neither speech nor normal affective ex-
and also deep brainstem sites including the pressions generated by an entire brain is
parabrachial nucleus in the pons. These dis- merely a brainstem reflex when forebrain
tributed “liking” sites are all connected systems determine them via hierarchical
together so that they interact as a single control.
integrated “liking” system, which operates When brainstem is connected to the fore-
by largely hierarchical control rules. brain, the entire affective system operates
in a hierarchical, flexible, and complex
fashion. In a neural hierarchy, forebrain
C. Pleasure Brain Hierarchy
operations overrule brainstem elements,
Certain elemental reaction circuits and dictate the output of the whole system.
within brain affective systems are contained This means that brainstem reflex aspects of
in the brainstem. By themselves, brainstem affective reactions are largely an artifact of
circuits have a basic autonomy in the sense brainstem isolation in decerebrates and
of functioning as simple reflexes when they anencephalics. In a fully connected brain,
have no other signals to modulate them. For affective “liking” and “disliking” reactions
example, basic positive or negative facial are determined by an extensive forebrain
expressions are still found in human anen- network, and the final behavioral expres-
cephalic infants born with a midbrain and sion of affective taste reactivity reflects fore-
hindbrain, but no cortex, amygdala, or brain “liking” processes.
classic limbic system, due to a congenital
defect that prevents prenatal development
D. Forebrain Limbic Hedonic Hot Spot
of their forebrain. Yet, sweet tastes still elicit
in Nucleus Accumbens
normal positive affective facial expressions
from anencephalic infants, and bitter or One forebrain hedonic island able to
sour tastes elicit negative expressions cause “liking” is an opioid hot spot in the
(Steiner, 1973). Similarly, a decerebrate rat nucleus accumbens. The nucleus accum-
has an isolated brainstem because a surgi- bens contains major subdivisions called
cal transaction that separates the brain- core and shell. While the core appears espe-
stem’s connections from the forebrain, but cially important for learning about rewards,
the decerebrate brainstem also remains able the shell is more important for generating
to generate normal taste reactivity expres- actual affective and motivational compo-
sions to sweet or bitter tastes placed in the nents of rewards themselves, including the
decerebrate’s mouth (Grill and Norgren, pleasure gloss of “liking” for food rewards
1978a). (Fig. 1).
However, brainstem generation of basic The shell of nucleus accumbens is an L-
reactions does not mean “liking” lives only shaped structure: its vertical back (called
196 8. BRAIN REWARD SYSTEMS FOR FOOD INCENTIVES AND HEDONICS IN NORMAL APPETITE
Positive hedonic Negative aversive
“liking” “disliking”
Nucleus accumbens
shell
Ventral pallidum
Opioid hedonic hot Spots
FIGURE 1 “Liking” reactions and brain hedonic hot spots. Top: Positive hedonic “liking” reactions are elicited
by sucrose taste from human infant and adult rat (e.g., rhythmic tongue protrusion). By contrast, negative aver-
sive “disliking” reactions are elicited by bitter quinine taste. Lower: Forebrain hedonic hot spots in limbic struc-
tures where μ-opioid activation causes a brighter pleasure gloss to be painted on sweet sensation. Red/yellow
shows hot spots in nucleus accumbens and ventral pallidum where opioid microinjections caused the biggest
increases in the number of sweet-elicited “liking” reactions. Modified from Peciña and Berridge (2005) and Smith
and Berridge (2005).
medial shell), stands against the middle of entire nucleus accumbens, and in quite a
the brain in each hemisphere, and its number of other forebrain limbic structures
bottom horizontal foot points outward too (Cooper and Higgs, 1994; Kelley, 2004;
toward the lateral sides of the brain (the Kelley et al., 2005a; Levine and Billington,
core is held in the concave crook formed 2004; Yeomans and Gray, 2002). So if opioid
between vertical back and lateral foot). It is activation causes taste pleasure wherever
the medial shell, the vertical upright of it stimulates appetite for palatable food,
the L, which has received most attention then the widespread brain distribution of
in the search for pleasure generators—with appetite-promoting sites means the brain
success. has an extensive opioid pleasure network
The pleasure generator in the medial that stretches throughout much of the fore-
shell runs in part on opioid neurotransmit- brain. That happy possibility would give
ters. Opioids are natural brain neurotrans- every brain a really large hedonic causation
mitters, such as enkephalin, endorphin, and system for generating pleasure.
dynorphin, that act on the same receptors But alternatively, if opioid circuits of
as opiate drugs such as morphine or heroin. food hedonic (“liking”) versus motivational
Opioid neurotransmitters that activate the μ (“wanting”) functions are organized some-
type of opioid receptor appear particularly what differently from each other, then
important to causing food reward opioid activation might enhance taste
“wanting” and “liking.” pleasure at only some of the sites where it
An important fact about opioid neuro- stimulates appetite. In that case, we must
transmitters in food reward is that they grapple with a complexity in opioid psy-
stimulate eating behavior in nearly the chology and brain function. In other words,
III. UNDERSTANDING BRAIN REWARD SYSTEMS FOR FOOD “LIKING” AND “WANTING” 197
brain opioid activation might contribute to positive hedonic impact. That increase in
“liking” food and “wanting” food in differ- apparent pleasure-activating quality was
ent ways in different brain places. Under- reflected by dramatic increases in sucrose-
standing precisely how each opioid brain elicited facial “liking” expressions, which
region contributes psychologically is a often doubled or even tripled in number
demanding but also interesting task for above control levels. But the “liking”
affective neuroscientists. increase was anatomically restricted to a
This issue was more recently addressed single hedonic hot spot in the brain’s
in a hedonic mapping study by Susana medial shell of nucleus accumbens (Peciña
Peciña at the University of Michigan and Berridge, 2005). In rats, the hedonic hot
(Peciña and Berridge, 2005). It turns out that spot was roughly just a cubic millimeter in
only one relatively small site in the medial size, contained entirely in the rostral and
shell may generate food “liking” as an dorsal quadrant of medial shell. Inside the
opioid pleasure island or hedonic hot spot. hedonic hot spot, opioid activation made
That hedonic hot spot is in the rostral and sweet sucrose taste “liked” even more than
dorsal one-quarter of medial shell. Here, μ- normal, and made bitter quinine taste “dis-
opioid activation acts as a hedonic genera- liked” less (not as aversive)—shifting both
tor to paint a pleasure gloss on sweetness, positive/negative dimensions toward a
generating more “liking” for the food it also positive pole. Outside the hot spot, positive
makes more “wanted.” hedonic impact was no longer increased,
Peciña’s study used a “Fos plume” even though the “disliking” suppression
mapping technique to find where micro- zone extended more caudally. In fact, in one
injections of a drug that activates opioid posterior site outside the hedonic hot spot
circuits causes increased “liking” reactions affective suppression applied to both sweet
to the hedonic impact of a pleasant taste. To “liking” and bitter “disliking”—essentially
map pleasure generation, Peciña first made an affective cold spot of general suppres-
painless microinjections into rats’ brains of sion. Thus Peciña’s mapping of opioid
tiny droplets of a drug known as DAMGO, mechanisms indicates that a localized
which stimulates μ opioid receptors hedonic island in the medial shell of
(natural neurotransmitter receptors for nucleus accumbens helps generate the
heroin or morphine). The opioid drug pleasure gloss that opioid circuits paint
caused nearby neurons with appropriate onto sweet sensation to make it positively
receptors to begin transcribing genes on “liked.”
chromosomes in their cellular nucleus. One
1. Larger Opioid Sea of “Wanting” in
is a rapid-onset or immediate early gene
Nucleus Accumbens
called c-fos, which is transcribed to produce
a protein called Fos that plays important In addition to causing increased “liking,”
roles in subsequent neuronal function. Fos almost all opioid microinjections in nucleus
protein stains very dark in appearance accumbens also caused the rats to eat more
when postmortem brain slices are appro- food soon afterward, increasing “wanting”
priately processed later with chemicals and for food reward too, even outside the
antibodies that bind to the protein, and as a hedonic hot spot (and even in the suppres-
result the neurons with drug-induced Fos sive cold spot). The appetite-increasing
could be seen later as forming a dark plume zone was much larger than the pleasure hot
on a slice of brain tissue. The size of each spot: it was as though a large opioid sea of
microinjection plume showed how far in “wanting” in the shell of nucleus accum-
the brain its drug had acted. bens contains a smaller opioid island of
Some opioid drug microinjections “liking” for the same reward (Peciña and
caused sweet taste to carry increased Berridge, 2005).
198 8. BRAIN REWARD SYSTEMS FOR FOOD INCENTIVES AND HEDONICS IN NORMAL APPETITE
The large size of the opioid “wanting” lay outside the anterior and dorsal region of
zone fits with many earlier results from medial shell.
elegant appetite-mapping studies that have
3. Beyond Opioid “Liking”: Other Hedonic
shown that many limbic brain structures
Neurotransmitters in Nucleus Accumbens?
support opioid-increased eating of palat-
able sweet or fatty foods (Gosnell and Opioid activation is only one type of
Levine, 1996; Kelley et al., 2005b; Levine neurochemical signal received by neurons
and Billington, 2004; Will et al., 2003, 2004; in the shell nucleus accumbens. Are any
Zhang and Kelley, 2000). But the opioid others able to modulate “liking” reactions
“liking” island identified by Peciña indi- to food hedonic impact? The answer
cates that only in the rostral/dorsal hedonic appears to be yes.
hot spot does opioid activation in medial
4. Cannabinoid “Liking”
shell also increase “liking” reactions to food
at the same time as increasing “wanting” to Neurons in the nucleus accumbens also
eat. manufacture an endogenous cannabinoid
neurochemical called anandamide, the CB1
2. Implications for Normal Eating
receptors for which are activated by active
and Disorders
ingredient THC in the drug, marijuana.
So it seems that the same μ-opioid neu- Anandamide has been suggested to be a
rotransmitter stimulation does different reverse neurotransmitter, which would be
psychological things in different spots released by a target neuron in the shell to
within the same brain structure. This leads float back to nearby presynaptic axon
us to outline several speculative possibili- terminals.
ties by which eating disorders might relate Marijuana, in addition to its own central
endogenous opioid neurotransmission in rewarding effects, is widely known to cause
nucleus accumbens shell. an appetite-stimulating effect sometimes
First, one could speculate that patho- called the “marijuana munchies,” raising
logical overactivation in regions of the intake especially of palatable snack foods.
opioid hedonic hot spot might cause Several investigators have suggested that
enhanced “liking” reaction to taste pleasure endogenous cannabinoid receptor activa-
in some individuals. An endogenously tion stimulates appetite in part by enhanc-
produced increase in opioid tone there ing “liking” for the perceived palatability of
could magnify the hedonic impact of food (Cooper, 2004; Dallman, 2003; Higgs
foods, making an individual “like” food et al., 2003; Kirkham and Williams, 2001;
more than other people, and “want” to eat Kirkham, 2005; Sharkey and Pittman,
more. 2005).
A second and alternative speculative A more recent taste reactivity study by
possibility is that activation in the opioid Jarrett and Parker found that THC causes
sea of “wanting” outside the hedonic island increased “liking” reactions to sugar tastes
could cause people to “want” to overeat in rats, just as opiate drugs do (Jarrett et al.,
palatable, without making them “like” food 2005). Focusing on natural endogenous
more. If so, the preceding results would brain cannabinoids, a microinjection study
predict that this increased appetite would by Stephen Mahler and Kyle Smith in our
occur from excessive opioid function in a laboratory pinned the neural causation
relatively large region of nucleus accum- of cannabinoid “liking” on activation
bens shell. The resulting “wanting” to eat of natural anandamide receptors in the
would occur without any concomitant nucleus accumbens shell (Mahler et al.,
increase in the perceived palatability of 2004). Microinjections of anandamide
food if the major locus of elevated activity directly into the medial shell of nucleus
III. UNDERSTANDING BRAIN REWARD SYSTEMS FOR FOOD “LIKING” AND “WANTING” 199
accumbens promoted positive “liking” Of these various neurochemical signals,
reactions to the pleasure of sucrose GABA at least can potently alter “liking”
taste. reactions to the hedonic impact of sugar
The ability of natural anandamide to tastes. But the positive/negative valence of
magnify the hedonic impact of natural food GABA on “liking” versus “disliking”
reward raises interesting questions about depends very much on precisely where in
whether natural sensory reward functions the shell the GABA is (Reynolds and
will be disrupted in people by taking drugs Berridge, 2002). For example, GABAstimu-
that have been proposed to help dieters or lation in the anterior subregion of the shell
addicts suppress their excessive consump- can increase “liking” reactions as well as
tion by blocking the natural CB1 receptors food intake. GABAin most of the front half
for anandamide and other endogenous of the shell increases food intake without
cannabinoids (Cooper, 2004; Higgs et al., increasing “liking” reactions to hedonic
2003; Kirkham and Williams, 2004). The impact, a bit like opioid activation in much
answer is currently not known: the fact that of the shell described before. And GABA
a brain event can cause enhanced pleasure delivered to the posterior half of the shell
(i.e., sufficient cause for hedonic impact) dramatically suppresses intake, and makes
does not necessarily mean that the brain sweet tastes “disliked,” reversing their
mechanism is needed for normal pleasure usual hedonic impact (Reynolds and
(i.e., necessary cause for hedonic impact). Berridge, 2002).
The two questions must be separately It remains to be known whether similar
answered by future research. changes in “liking” are evoked by nucleus
In either case, it appears that the cannabi- accumbens glutamate blockade, by
noid pleasure zone overlaps with the opioid microinjections of a drug that blocks AMPA
hedonic hot spot described previously in receptor signals, and so which may simi-
medial shell of nucleus accumbens. That larly hyperpolarize neurons in medial shell.
suggests that both natural opioids and However, glutamate AMPA blockade does
natural cannabinoids act in overlapping alter eating behavior and food intake in
hedonic islands of the nucleus accumbens ways similar to GABA (Reynolds and
shell. In those overlapping zones, both neu- Berridge, 2003), which increases the plausi-
rochemicals act to enhance “liking” for bility that “liking” might be modulated by
the hedonic impact of natural sensory glutamate just as “wanting” is. The role of
pleasures. cortico-amygdala-hippocampal glutamate
This raises possibilities for potential signals to nucleus accumbens in modulat-
interactions between these two neurochemi- ing “liking” reactions to hedonic impact of
cal forms of pleasure gloss, opioid and sweetness is a topic of substantial interest.
cannabinoid (Vigano et al., 2005). And there
are additional “liking” interactions to con-
E. Ventral Pallidum: “Liking” and
sider too. Beyond neurotransmitters related
“Wanting” Pivot Point for Limbic Food
to classic drugs of abuse, other neurotrans-
Reward Circuits
mitters such as GABAare also used by the
same neurons in the medial shell. These Leaving the nucleus accumbens, output
neurons both send and receive GABA projections head to several destinations but
signals. In addition, these neurons receive the single heaviest projections are
further neurochemical inputs, such as glu-
posteriorly to two nearby neighbors, the
tamate from the neocortex, hippocampus,
ventral pallidum and lateral hypothalamus.
and basolateral amygdala, and dopamine
Of these two structures, the lateral hypo-
from mesolimbic neurons in the midbrain
thalamus has long been famous for roles in
ventral tegmental area.
food intake and food reward. Lesions of
200 8. BRAIN REWARD SYSTEMS FOR FOOD INCENTIVES AND HEDONICS IN NORMAL APPETITE
the lateral hypothalamus disrupt eating amygdala” for a bit behind that lies
and drinking behaviors, sending food and between ventral pallidum and lateral
water intakes to zero (Teitelbaum and hypothalamus.
Epstein, 1962; Winn, 1995). After electrolytic Ventral pallidum is the chief target of
lesions to lateral hypothalamus, rats would the heaviest projections emanating from the
starve to death unless they were given nucleus accumbens, and so it is the primary
intensive nursing care and artificial intra- output channel through which mesocorti-
gastric feeding. colimbic circuits must work (Zahm, 2000).
Decades ago, lateral hypothalamic The ventral pallidum is relatively new on
lesions were thought not only to abolish the affective neuroscience scene, but there is
food “wanting,” but also to abolish food reason to believe this chief target of nucleus
“liking” too. Even sweet tastes were accumbens is crucial for both normal
reported to elicit bitter-type disliking reac- reward “liking” and for enhanced “liking”
tions (Schallert and Whishaw, 1978; Stellar caused under some neurochemical
et al., 1979; Teitelbaum and Epstein, 1962). conditions.
However, it appears that lateral hypothala- An astounding fact is that the ventral
mus may have been blamed through a case pallidum is the only brain region known so
of mistaken identity for the effects of lesions far where the loss of neurons is capable of
that stretched beyond it in lateral and ante- abolishing all “liking” for sweetness. It is
rior directions. Early studies on this topic the only brain site absolutely necessary for
indicated that sucrose “liking” would be normal sucrose “liking” in the sense that
replaced by sucrose “disliking” only if the damage to it makes “liking” go away (at
lesion were in the anterior zone of lateral least for several weeks). Sucrose no longer
hypothalamus—and not if the lesion were elicits “liking” reactions from a rat that has
in the posterior part of lateral hypothala- an excitotoxin lesion of its ventral pallidum,
mus, where it would produce loss of eating a type of lesion that selectively destroys the
and drinking, but leave “liking” reactions neurons that live in that structure while pre-
essentially normal (Schallert and Whishaw, serving fibers from neurons elsewhere that
1978). Further lesion studies by Cromwell are simply passing through. Instead sucrose
mapped more carefully the boundaries of taste elicits only “disliking” reactions after
sites where neuron death caused aversion, the ventral pallidal lesion, as though the
and found that the “disliking” lesions sweet taste had become bitter quinine
might actually have to be so far anterior and (Cromwell and Berridge, 1993).
lateral that they actually were outside the Ventral pallidum can also generate
lateral hypothalamus itself—and in another enhancement of natural pleasure, at least
structure, now called the ventral pallidum when it is intact. Ventral pallidum contains
(Cromwell and Berridge, 1993). its own hedonic hot spot where μ opioid
Until about 10 years ago the ventral pal- activation can increase the pleasure gloss
lidum was known often as the substantia that gets painted on sweetness. In a hedonic
innominata, or brain structure without a mapping study, Kyle Smith discovered that
name, and earlier than 20 years ago it was opioid DAMGO microinjections into a
often mistaken for part of the lateral hypo- hedonic hot spot within the posterior VP
thalamus, as we have seen. Today it has a caused sucrose to elicit over twice as many
name, actually several names that corre- “liking” reactions than it normally did
spond to different divisions of this intrigu- (Smith and Berridge, 2005). Opioid activa-
ing part of the ventral forebrain. The chief tion in the posterior ventral pallidum
names today are “ventral pallidum” for the increased the hedonic impact of the natural
part known to cause “liking” for sensory taste reward, and also caused rats to eat
pleasure, and “sublenticular extended over twice as much food. The hedonic hot