Role of brain dopamine in food reward
Roy A. Wise*
Intramural Research Program, Department of Health and Human Services, National Institute
on Drug Abuse, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA
The ability of food to establish and maintain response habits and conditioned preferences depends
largely on the function of brain dopamine systems. While dopaminergic transmission in the nucleus
accumbens appears sufficient for some forms of reward, the role of dopamine in food reward does not
appear to be restricted to this region. Dopamine plays an important role in both the ability to energize
feeding and to reinforce food-seeking behaviour; the role in energizing feeding is secondary to the
prerequisite role in reinforcement. Dopaminergic activation is triggered by the auditory and visual as
well as the tactile, olfactory, and gustatory stimuli offoods. While dopamine plays a central role in the
feeding and food-seeking of normal animals, some food rewarded learning can be seen in genetically
engineered dopamine-deficient mice.
Keywords: food; reward; reinforcement; dopamine
While the cognitive and behavioural disturbance we
call ‘hunger’ is innate, the appetites for specific foods
are learned. Undifferiented hunger is controlled largely
by fluctuations of peripheral and hypothalamic
peptides (Saper et al. 2002; Horvath & Diano 2004)
and thirst is controlled by fluctuation in vagal input
(Kraly et al. 1975) triggered by hypovolemia (Fitzsi-
mons 1961) and by dehydration of cells in the lateral
preoptic area of the hypothalamus (Blass & Epstein
1971; Peck & Novin 1971), However, neither hunger
nor thirst results in unconditioned goal-directed
behaviour (Changizi et al. 2002). Chance encounters
with the sweet (Pfaffmann 1960) or salty (Denton
1982) taste of preferred foods or with the oral cooling
by ingested fluids (Mendelson & Chillag 1970; Freed &
Mendelson 1974) are required before goal-directed
behaviour results from the interaction of internal need
states with the salience of environmental cues (Bindra
1972). The infant recognizes (Steiner et al. 2001) and
can learn to seek out (Johanson & Hall 1979) sweet
tastants, but the appetite for a specific food is
controlled by the interaction of the hunger-associated
peptide levels with the brain circuitry that codes the
animal’s reinforcement history with that food. Until it
has received reinforcing feedback from various foods,
the infant indiscriminately mouths both food and non-
food objects. The monkey’s appetite for a yellow
banana depends on the prior learning of the association
of the sight of the yellow banana skin with the sweet
taste of the white banana meat (Wise 2004b) and with
the post-ingestive consequences of the ingested fruit
(Le Magnen 1959). Similarly, the vitamin-deficient rat
does not innately know what foods contain the deficient
vitamin. Rather, the vitamin-deficient rat progressively
loses its food neophobia until, by sampling new foods
randomly, it chances on and ingests a food with the
missing vitamin (Rodgers & Rozin 1966; Rozin &
Rodgers 1967; Rozin 1969). The specific preference
for a particular substance is only established when the
post-ingestional consequences of the repleting food
stamp in or ‘reinforce’ the tendency to approach that
food (Rozin & Kalat 1971). Similarly, food- or water-
seeking behaviours develop only after the animal has
had the paired experience of hunger with eating or
thirst with drinking, respectively (Changizi et al. 2002).
Our understanding of the brain circuitry through
which various rewards control behaviour began with
the findings that rats would learn to work for the direct
electrical stimulation of the brain (Olds & Milner 1954)
or for the pharmacological stimulation of the brain by
psychomotor stimulant drugs (Pickens & Harris 1968).
The finding that the rewarding effects of brain
stimulation (Liebman & Butcher 1974; Fouriezos &
Wise 1976) and of psychomotor stimulants (Yokel &
Wise 1975; de Wit & Wise 1977) was blocked or
attenuated by dopamine antagonists first implicated
brain dopamine in reward function. Similar attenu-
ation of food reward by dopamine antagonists (Wise
et al. 1978a,b) first implicated brain dopamine in the
control of behaviour by natural rewards.
2. IMPORTANCE OF DOPAMINE FOR
Dopamine antagonists impair learning (Wise &
Schwartz 1981) and, by extinguishing them, previously
learned (Wise et al. 1978a,b) instrumental responding
for food. Several lines of study confirm that they do so
by blunting reward function itself (Wise 1982, 2004a;
Beninger 1983; Smith 1995) rather than, as has been
suggested (Mason et al. 1980; Koob 1982; Tombaugh
et al. 1982; Salamone 1986), by simply impairing
Phil. Trans. R. Soc. B (2006) 361, 1149–1158
Published online 15 June 2006
One contribution of 16 to a Theme Issue ‘Appetite’.
q 2006 The Royal Society
The earliest evidence that dopamine plays an
important role in motivational function was that brain
stimulation and psychomotor stimulants were simply
ineffective as reinforcers in animals treated with
response-sparing doses of dopamine antagonists.
Intravenous amphetamine and cocaine failed to
maintain responding when tested under the influence
of dopamine antagonists, despite evidence of adequate
response capacity. Indeed, in this case animals respond
at higher than normal rates before ceasing to respond
following pretreatment with dopamine antagonists
(Yokel & Wise 1975, 1976; de Wit & Wise 1977;
Ettenberg et al. 1982).
In the case of brain stimulation reward, responding
is generally lower when animals are treated with
dopamine antagonists; however, several conditions
reveal that the low response rates are due to
ineffectiveness of the reinforcer and not incapacitation
of the animal. First, responding decreases pro-
gressively, both within sessions and across sessions,
in animals pretreated with dopamine antagonists
(Fouriezos & Wise 1976; Fouriezos et al. 1978;
pretreated with moderate doses of dopamine antagon-
ists are required to traverse an alleyway for access to the
response lever that delivers the stimulation, per-
formance is initially normal and deteriorates after
several trials. Moreover, lever-pressing in the goal box
deteriorates before running speed or latency to leave
the start box; thus brain stimulation loses its ability to
maintain responding in the goal box before the animals
stop running to obtain it (Fouriezos et al. 1978).
Second, after animals have stopped responding for
brain stimulation reward under conditions of dopa-
mine blockade, a reward-predicting environmental
stimulus can, temporarily, reinstate normal per-
formance; thus it appears that the decrement in
responding results from the progressive loss of the
expectancy of reward rather than from the immediate
loss of response capacity (Fouriezos & Wise 1976;
Franklin & McCoy 1979; Gallistel et al. 1982). Finally,
when animals are tested in a ‘rate–frequency’ paradigm
(an analogue of a dose–response paradigm), it is the
stimulation frequency required to motivate the animal,
rather than the maximum response rate that can be
obtained from the animal, that is altered by dopamine
blockade; animals can respond normally, but they
require a higher stimulation ‘payoff’ if they are to keep
doing so (Franklin 1978; Gallistel & Karras 1984).
Finally, if dopamine-blocked rats are trained to earn
rewarding brain stimulation in two ways (traverse a
runway or press a lever) and are then tested in the two
tasks sequentially, the animals initiate responding
normally in the second task despite having ceased to
respond normally in the first task; thus response
capacity in the second task is unimpaired despite
cessation of responding in the first task (Gallistel et al.
1982). Thus, while performance may be partially
impaired by treatment with dopamine antagonists,
data from several paradigms confirm that these drugs
attenuate the ability of the stimulation to sustain
normal performance before they interfere with the
animal’s capacity to generate such performance.
3. IMPORTANCE OF DOPAMINE FOR FOOD
The concept of reinforcement is, at its core, a concept
of how stimulus (Pavlov 1928) and response (Thorn-
dike 1933) associations are formed and how they serve
as the basis of habit acquisition (Skinner 1938). Food
does not serve as a normal reinforcer in animals
pretreated with dopamine antagonists; such treatment
causes, for example, a dose-dependent decrease in how
quickly animals learn to lever-press for food (Wise &
Schwartz 1981). Under pretreatment with low doses of
the dopamine antagonist animals eventually reach the
normal performance asymptote; however, they require
more trials to do so. With higher pretreatment doses
learning is slower and may not reach the same
performance asymptote. With yet higher doses there
is no evidence of learning.
While the concept of reinforcement is most fre-
quently used to explain response learning (Thorndike
1933; Skinner 1935; Hull 1937), it was first used in
relation to stimulus learning (Pavlov 1928). Stimulus
learning is now known to contribute significantly to
response learning (Rescorla & Solomon 1967; Bindra
1972) and dopamine is thought to play a role in both
(Wise 1989). Most studies of the reinforcing efficacy of
food reward deal with the ability of the reward to
maintain rather than to establish instrumental
behaviour; without reinforcement both stimulus associ-
ations (Pavlov 1928) and response associations
(Skinner 1933) extinguish.
When well-trained animals are tested under the
influence of dopamine antagonists, food loses the
ability to maintain normal responding. Whereas
normal responding is initiated, responding slows
progressively both within sessions and across sessions
(Wise et al. 1978b; Dickinson et al. 2000). Similar
progressive loss, both within and across trials, can be
seen in the ability of food to maintain free feeding
(Wise & Raptis 1986). The response slowing resembles
what is seen in extinction conditions (when the normal
reward is withheld), and is generally interpreted as a
reflection of the impoverishment or ‘devaluation’ of
food reward in the dopamine-impaired animal (Wise
et al. 1978a,b; Xenakis & Sclafani 1981, 1982; Geary &
Smith 1985). (See Salamone et al. (2005) for a
dissenting opinion and Wise (2004a) for rebuttal.)
Few alternative hypotheses have been offered to
explain the progressive response deficits seen when
animals are tested under conditions of dopamine
blockade. There is the suggestion that the progressive
deficit might reflect a susceptibility to fatigue (or some
other progressive within-trial performance impair-
hypothesis can be ruled out from a variety of findings.
First, the deficits are not only progressive within-trials;
responding decreases progressively across repeated
tests that are spaced days apart, with normal levels of
responding between the days when the dopamine
antagonist is given (Fouriezos et al. 1978; Wise et al.
1978b; Wise & Raptis 1986). Second, animals trained
under intermittent dopamine blockade, like animals
under intermittent reinforcement, respond more, not
less, when tested for habit strength during extinction
trials (Ettenberg & Camp 1986). There is no suggestion
1150R. A. Wise
Dopamine and food reward
Phil. Trans. R. Soc. B (2006)
of any fatigue-like effect in this paradigm. Finally, when
animals are trained in single daily trials to traverse a
runway for food, dopamine blockade does not interfere
with latency or running speed on the trial when the
dopamine antagonist is given; rather, performance is
impaired only on the following day, when the animals
are free of the antagonist (McFarland & Ettenberg
1998). Fatigue due to dopamine blockade can explain
neither the normal performance on the treatment day
nor the slow performance on the day after treatment;
here performance is impaired by the animal’s memory
of the previous day’s experience and not by the
pharmacological treatment itself.
Another suggested alternative for the progressive
within-trial slowing of feeding and responding for food
was that the slowing reflected the effects of enhanced
satiety rather than the effects of blunted reward. This
suggestion has been falsified in three ways. First, the
same within-session progressive deficits are seen when
dopamine-blocked animals are offered non-nutritive
saccharin as when they are offered nutritive food
reward; no such deficits are seen in control animals
that do not receive the dopamine antagonist (Wise et al.
1978a). Second, within-session progressive deficits are
seen when ingested sucrose is not absorbed but is,
rather, drained through an open gastric fistula
(Geary & Smith 1985). Third, the satiety hypothesis
(like the fatigue hypothesis) cannot explain the fact that
performance decreases across successive tests as a
function of how much experience the animal has
previously had with food in the dopamine-blocked
condition (Wise et al. 1978b; Wise & Raptis 1986) and
not as afunction of experience with dopamine blockade
in the absence of food (Wise et al. 1978b). Thus, it
appears to be the memory of the food experience in the
dopamine-blocked condition, not the experience of
dopamine blockade itself, that determines the decline
in responding between trials in the dopamine-blocked
When animals are tested with a number of sucrose
concentrations, dopamine-blocked animals respond to
a given concentration as if it were weaker than normal
(Xenakis & Sclafani 1981; Geary & Smith 1985; Bailey
et al. 1986; Schneider et al. 1986, 1990). Thus, normal
sucrose lick rates are shown in dopamine-blocked
animals if the concentration of the sucrose solution is
increased to 10% from the normal 5%. The devalua-
tion of sucrose reward—the treatment of high concen-
trations as if they were lower—is seen either in animals
pretreated with either D1- or D2-type dopamine
receptor blockade (Schneider et al. 1986). Thus, like
many dopamine-mediated behaviours (Clark & White
1987), performance for sweet reward appears to
require co-activation of D1- and D2-type receptors.
The hypothesis that dopamine transmission is
important for food reward implies that food reward
elevates dopamine levels, as do,for example, some drug
rewards (Hurd et al. 1989; Pettit & Justice 1989; Wise
et al. 1995a,b; Ranaldi et al. 1999). Indeed, food reward
(Hernandez & Hoebel 1988) and food reward-
associated stimuli (Bassareo & Di Chiara 1999) do
elevate dopamine levels in the nucleus accumbens.
Indeed, just as m and d opiate agonists are rewarding in
proportion to their ability to elevate dopamine levels
(Devine et al. 1993; Devine & Wise 1994), so are
different sucrose concentrations rewarding in pro-
portion to their ability to elevate dopamine levels in
the nucleus accumbens (Hajnal et al. 2004).
4. RECENT ISSUES
An important role for dopamine in reward function has
been well established for many years, but several fine
points continue to be discussed in the literature. Is
dopamine absolutely necessary for reward? Is dopa-
mine more important for the expectancy of reward
before it is delivered or for the impact of reward after it
is delivered? Is the dopamine in nucleus accumbens
more important for reward than the dopamine in other
brain regions? Some of these recent issues are best
resolved by consideration of the early literature.
First, studies involving pharmacological blockade of
dopamine receptors have suggested a necessary role for
dopamine in the reward function (Wise & Rompre ´
1989; Wise 2004a). Recent studies with genetically
engineered mice challenge this strong position. First,
deletion of the tyrosine hydroxylase (TH) gene with
rescue of noradrenergic function results in mice that
are born superficially normal and eat and gain weight
for 10–15 days, at which time their eyes normally open
and they begin nibbling and foraging for solid food.
Unless treated with L-DOPA, they then lose weight,
usually dying by 4 weeks of age (Zhou & Palmiter
1995). If treated with L-DOPA, however, they are alert
and active for about 8 h after their daily treatment,
eating enough during this period to maintain them-
selves (Szczypka et al. 1999). Restoration of TH
expression in the caudate nucleus but not in the
nucleus accumbens is sufficient to restore normal
feeding in the TH knockout animals (Szczypka et al.
If these dopamine-deficient mice are maintained by
daily L-DOPA treatment but tested when showing
Parkinsonian akinesia, 18 or 28 h after the previous
L-DOPA maintenance injection, they show normal
sucrose and saccharin preferences over water, and
drink more of these solutions than water in single bottle
tests even after anytrace levels of residual dopamine are
purged by treatment with the dopamine-releaser
amphetamine (Cannon & Palmiter 2003). Such
animals show between-session (but not within-session)
learning in a water escape task (Denenberg et al. 2004).
If aroused with caffeine, such animals can learn a side-
preference (but not reverse it) for food reward in a
T-maze (Robinson et al. 2005). These findings establish
that, whatever its importance in normal animals,
normal dopamine function is not an absolutely
necessary condition for rudimentary instrumental
Another recent issue is whether dopamine is
important for the motivation to seek anticipated food
or rather for the reinforcing effects of food once it has
been earned and received (Berridge & Robinson 1998;
Salamone & Correa 2002). Food rewards have both
kinds of effect (Wise 1989, 2004b). The primary effect
would appear to be the ability to reinforce learning, as
evidenced by: (i) the fact that animals do not learn
food-seeking responses when their dopamine systems
Dopamine and food reward
R. A. Wise1151
Phil. Trans. R. Soc. B (2006)
are blocked (Wise & Schwartz 1981); (ii) the fact that
the effects offinding a piece offood when the dopamine
system is blocked are more evident on the day after the
dopamine blockade than on the day of the dopamine
blockade (McFarland & Ettenberg 1998); and (iii) the
fact that food-seeking habits extinguish when animals
are tested under dopamine blockade (Wise et al.
However, secondary to its role in the reinforcement
history of the animal, dopamine clearly does have a role
in the motivation of reward-seeking behaviours. While
food-seeking is thought to be initiated by hunger, it is
food-predictive or ‘incentive–motivational’ environ-
mental cues in the environment that release and
guide the behaviour. The incentive–motivational sal-
ience of these stimuli depends upon the prior
dopamine-dependent reinforcement of their associ-
ation with the reward. Again, the McFarland &
Ettenberg (1998) study clearly illustrates the point.
Their trained animals left the start box promptly
and ran the runway quickly except on the day after
they obtained food in the goal box while under the
influence of the dopamine antagonist haloperidol.
Thus incentive–motivation—the process by which
reward-predictive cues activate and motivate an
animal—depends on a dopamine-dependent history
of association (reinforcement) between the cues and
the reward they predict.
In addition, a ‘priming’ presentation of a reward
sample (rather than of a conditioned predictor) can
arouse an animal and motivate it to seek more of the
priming stimulus. Salted peanuts and potato chips are
good examples of rewards that are particularly good at
priming further reward-seeking. A taste of such
rewards is particularly effective at renewing reward-
seeking behaviours after they have been given-up
because they are no longer rewarded (Skinner 1938).
Administering dopamine agonists is among the most
effective ways to reinstate extinguished reward-seeking
(de Wit & Stewart 1981, 1983; Wise et al. 1990).
Questions about the role of dopamine in reward
function have also arisen from evidence that dopamine
seems unimportant for the facial responses to oral
presentation of sweet tastants (Berridge et al. 1989;
Pecina et al. 1997). If one was to assume correspon-
dence between the facial expression of ‘liking’ food and
the ability of that food to serve as a reinforcer, this
finding would pose a challenge to the view that
dopamine is important for the ability of food to stamp
in stimulus and response associations. The assumption
of correspondence between the facial expression of
liking and the hedonic response to reinforcement is,
however, open to serious question.
Initial studies of the orofacial responses of humans
to various tastants identified unique reactions to sweet,
sour, and bitter stimuli (Steiner 1973). In rodents, the
reactions to sweet and bitter stimuli are clearly
distinguishable and have been classified as ‘ingestive’
and ‘aversive’ fixed action patterns (a misnomer, as it is
the stimulus, not the action pattern, that is aversive)
(Berridge & Grill 1984). The rodent orofacial
responses to sweet and bitter tastants are, essentially,
the licking of lips associated with the acceptance of a
fluid and the gagging and chin-rubbing associated with
fluid rejection, respectively. Following Schneirla’s
(1959) argument that approach and withdrawal
responses are the only objective terms applicable to
all motivated behaviour in all animals, Berridge &
Robinson (2003) have suggested that these oral fixed
action patterns reflect the hedonic assessments—liking
or disliking—of various tastants. What is not clear,
however, is how well the fixed action patterns of
ingestion and rejection, expressed in decorticate rats
(Grill & Norgren 1978; Hall & Bryan 1981) and
anencephalic children (Steiner 1973), correlate with
the higher-level subjective hedonic responses to and
objective reinforcement induced by various foods.
The recent arguments of Berridge & Robinson
(1998) that dopamine is important for the wanting of
rewards but not the liking of rewards is based on several
assumptions about the relation of the taste reactivity
test to generalized emotional states. First, there is the
assumption that the brainstem reactions to taste stimuli
determine the hedonic response to those stimuli
(Berridge 2000). This assumption begs the question
of how humans learn to like bitter tastants like coffee
and broccoli. Second, there is the assertion that the
liking of a tastant need not be conscious (Berridge &
Robinson 1998; Berridge & Winkielman 2003); in this
view, whether the subject likes or dislikes a tastant is
more directly evident to an outside observer than to the
subject itself. This may well be true, but the possibility
raises the question of why subjective lay terms like
‘wanting’ and ‘liking’ should be substituted for the
more traditional motivational labels ‘drive,’ ‘incentive–
motivation’ and ‘reinforcement.’ Third, there is the
implicit assumption that all rewards are pleasant; this
assumption is falsified by the fact that animals can be
trained to work for aversive footshock (Kelleher &
Morse 1968) and that initial injections of heroin, while
extremely habit-forming, are often reported to be
aversive (Haertzen 1966). Finally, there is the assump-
tion that the mechanism of wanting and liking of
tastants can be generalized to other rewards such as
sexual interactions and addictive drugs (Robinson &
In order to see the relevance of subjective wanting
and liking for the behavioural control by the motivating
and reinforcing effects offood reward, it is important to
distinguish between the wanting and liking of an
abstract concept such as ‘sweets’ and the wanting and
liking of a specific food morsel that is currently
available to the peripheral senses. While Berridge &
Robinson (2003) hold that youcan both want and like a
given tastant (like chocolate fudge) at the same time,
you cannot experience at the same time the wanting
and liking of a given specific morsel of food. If you do not
yet have the morsel you can want it without knowing for
certain that you will like it; if you have it in your mouth
you can like it but it is no longer available to want.
Inasmuch as it is a real morsel and not an imagined
category that controls behaviour at a given time, we
can, for behavioural analysis, identify wanting with the
state of mind of an animal prior to earning a given food
morsel and identify liking as the state of mind once the
reward has been earned and is being sensed. From this
perspective, the animals in the McFarland & Ettenberg
(1998) study discussed above want the food pellet
1152R. A. Wise
Dopamine and food reward
Phil. Trans. R. Soc. B (2006)
before they have tasted it on the haloperidol treatment
day. If there is a deficit in the wanting of food in these
animals, it is a deficit in wanting the next pellet, the one
offered on the day after the pellet eaten during
haloperidol treatment. In as much as the animals ran
normally on the haloperidol treatment day and failed to
do so on the day following the haloperidol treatment, it
seems an inescapable conclusion that they wanted the
food despite dopaminergic dysfunction. This separ-
ation offood-seeking into discrete trials allows us to see
that haloperidol treatment disrupts food-seeking only
after the animal has had the opportunity to taste the
food under the influence of the dopamine blocker. As
discussed above, it would appear that the importance of
dopamine for the wanting of food on a given day
exposure results from the role dopamine played in the
prior liking of food on earlier exposures (whether it be
days, trials, morsels, or bites). It is the prior liking of (or
reinforcement by) a foodstuff—a dopamine-dependent
function—that establishes a subsequent cravingfor that
foodstuff (Rozin & Kalat 1971).
Another challenge of the view that dopamine plays
an important role in food reinforcement stems from the
unwarranted assumption that all the reward-relevant
dopamine functions occur in nucleus accumbens
(Salamone et al. 2001). While a good deal of work
implicates nucleus accumbens in the rewarding effects
of psychomotor stimulants (Roberts et al. 1977;
Ikemoto et al. 1997; Roberts et al. 1980), and while it
is nucleus accumbens dopamine fluctuations, for the
most part, that have been correlated with drug reward
and food reward (Di Chiara & Imperato 1988;
Hernandez & Hoebel 1988; Hurd et al. 1989; Pettit &
Justice 1989; Wise et al. 1995a,b; Ranaldi et al. 1999;
Bassareo & Di Chiara 1999), and while protein
synthesis in nucleus accumbens impairs instrumental
learning for food reward (Baldwin et al. 2002), it
nonetheless remains the case that lesions of the
dopamine projection to nucleus accumbens do not
cause feeding deficits (Ungerstedt 1971; Ervin et al.
1977), while lesions of the dopamine projections to the
dorsal striatum do (Ungerstedt 1971). Moreover, it is
genetic restoration of dopamine function in the dorsal
striatum, not in nucleus accumbens, that rescues
(Szczypka et al. 2001). While lesions of nucleus
accumbens disrupt cocaine self-administration more
than they disrupt heroin self-administration (Pettit
et al. 1984), ventral tegmental lesions that damage
nigrostriatal as well as mesolimbic fibres disrupt both
behaviours (Bozarth & Wise 1986). While nucleus
accumbens injections of opiates (Olds 1982; Goeders
et al. 1984) or psychomotor stimulants (Hoebel et al.
1983; Carlezon et al. 1995; Carlezon & Wise 1996;
Ikemoto et al. 1997) are rewarding, injections of
cocaine into the medial prefrontal cortex (Goeders &
Smith 1983, 1986) or olfactory tubercle (Ikemoto
2003), or injections of opiates into the ventral
tegmental area (Bozarth & Wise 1981; Devine &
Wise 1994; Zangen et al. 2002), are also rewarding.
Thus, nucleus accumbens is not the exclusive seat of
dopamine-dependent reward function, and nucleus
accumbens lesions should not be expected to disrupt all
Another recent issue is whether activation of
dopamine neurons represents reward, prediction of
reward, or an error signal reflecting the difference
between earned and expected reward. The issue arises
from electrophysiological studies of Schultz and
collaborators, suggesting that dopaminergic neurons
respond to rewards as long as they are not fully
predictable, but transfer to conditioned stimuli pre-
dicting reward once the predictivesignificance has been
learned (Schultz 1986; Romo & Schultz 1990;
Ljungberg et al. 1991, 1992; Schultz et al. 1993). It is
naive, of course, to expect that dopamine would play a
specialized role in only one of these functions.
Moreover, Schultz’s (Schultz 2002) distinction
between ‘reward-predicting’ and ‘rewarding’ stimuli
in these studies merits closer analysis. First, the
rewarding event is not consistently defined in the
various studies of Schultz’s monkeys. In these studies,
the reward was sometimes identified with presentation
of the rewarding object rather than with the oral
contact with the reward or with the post-ingestional
consequences of that reward that truly constitute the
rewarding event. In some studies, the primary reward-
ing stimulus was a piece of apple presented in a cup at
arm’s reach; in others it was a drop of fruit juice
presented in a spout near the animal’s mouth. In the
case of the juice, the rewarding eventwas assumed to be
the delivery of the juice rather than the taste of the
juice; presumably, in this case, latencies were short
enough that the presentation of the reward and the
tasting of the reward were almost concurrent. In the
case of pieces of apple, however, dopamine responses
were noted when the monkey touched the food and
again when the monkey tasted the food. Here, the
tactile rather than the taste contact was taken as the
rewarding event. Whether receipt of reward was
defined by the touch of the apple pieces or the delivery
of the juice, dopamine neurons responded to what was
designated as the rewarding event in early stages of
training but to what was designated as the reward-
predicting event (sound and sight of latch opening in
the case of the apple reward and sight of illumination of
a light cue in the case of the juice reward) and not, after
a great deal of training (thousands of training trials) to
the ‘reward’ itself.
Clarification of the influence of training in these
studies comes from subsequent studies in which the
effectiveness of the reward-predictive cues was varied.
When visual or auditory cues, or both, predicted
reward with 100% certainty,the responses of dopamine
neurons shifted from the reward itself (as defined
above) to the reward-predictive environmental stimuli
(Schultz 1986; Romo & Schultz 1990; Ljungberg et al.
1991, 1992; Schultz et al. 1993; Fiorillo et al. 2003). In
the case where presentation of the reward was
predicted by both auditory and visual stimuli, the
responses of dopamine neurons to the reward-predictor
(latch-opening) wasweakened when the visual stimulus
(sight of the door) was occluded (Schultz 1986). When
a visual stimulus predicted reward with 75, 50, or 25%
probability, responsiveness to the visual stimulus
decreased and responsiveness to the tactile or taste
stimulus increased accordingly (Fiorillo et al. 2003).
This finding suggests the need for a closer examination
Dopamine and food reward
R. A. Wise1153
Phil. Trans. R. Soc. B (2006)
of the distinction between reward and reward-prediction
(Wise 2004b). While food might be considered a
‘primary’ reward (Schultz 1986), food is identified by
each of the five senses and it is only in the taste of sweet
foods (and perhaps the taste of salt in the case of
sodium deficiency; Quartermain et al. 1967) that a
strong argument can be made that the sensory
experience of food is innately rewarding (Steiner
1974; Hall & Bryan 1981) in the absence of learned
association with its post-ingestive consequences
(Le Magnen 1959; Rozin & Kalat 1971; Messier &
White 1984; Sclafani 2004). To the degree that it is the
post-ingestional effects of a food that is reinforcing,
however, as is the case with the rewarding effects of
minerals or vitamins for deficient animals, the sensory
experience of a given foodstuff becomes a reinforcer in
its own right: a conditioned reinforcer (Robbins 1978).
Certainly, the touch of a piece of apple is a learned
reinforcer for Schultz’s very well trained monkeys
(Schultz 1986), as, it would appear, are the click or
sight of the opening door behind which food is to be
found (Schultz 1986). Even the sweet taste of saccharin
appears to be a learned reward (Messier & White
1984). Thus, Schultz’s distinction between reward-
predictors and primary reward is fuzzy distinction; the
visual or auditory awareness of the availability of food,
if it is a 100% predictor, is certainly as primary as the
tactile awareness of that availability, and it is arguably
as primary as the olfactory or gustatory awareness of
foods that satisfy a mineral deficiency. The fact that
dopamine neurons no longer fire in response to the
taste of apple when that taste has been predicted by the
feel of the apple or the click that predicts the feel is
completely consistent with the fact that food-predicting
stimuli can become conditioned reinforcers in their
own right so long as dopamine function is not
impaired during the association of the conditioned
stimulus with the food (Beninger & Phillips 1980;
Taylor & Robbins 1986).
This does not negate the fact that the phasic
activation of dopamine neurons occurs in proportion
to the discrepancy between the expected reward and
the observed reward, or that such information partici-
pates in the learning associated with reinforcement. It
should be noted, however, that the short-latency
activation of dopamine neurons by visual stimuli occurs
before the eye moves to fixate a peripheral visual
stimulus. Thus dopamine neurons are likely to be only
reporters of the discrimination made by the inferior
colliculus between reward-predictive or otherwise
salient stimuli and various stimulus events that bear
no relation to rewarding events (Dommett et al. 2005).
5. CONCLUSIONS AND PERSPECTIVES
Brain dopamine plays several roles in the ability offood
to serve as a reward. It is important—but apparently
not completely necessary—for the reinforcement
function of rewards, their ability to stamp in stimulus
and response associations. Current evidence suggests
that dopamine in the caudate nucleus may play a
more important role than dopamine in the nucleus
accumbens in the reinforcement of response habits
(White & McDonald 2002; Wise 2004a). Past
dopamine-dependent reinforcement of stimulus–
reward associations is, in turn, important for the
incentive–motivational energizing effect of reward-
predictive cues in the environment. And, of course,
some degree of basal dopamine is important for
rudimentary behaviour of any kind (Hornykiewicz
1979; Stricker & Zigmond 1985). This does not
mean that dopamine plays a specialized or exclusive
role in reward function. Other neurotransmitter
systems are certainly involved and it is not clear what
subsets of dopamine neurons contribute to reward
function. Reward function—and food reward in
particular—is only one of the many functions in
which dopamine plays an important contributing role.
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