Elsevier

Brain Research Reviews

Volume 28, Issue 3, December 1998, Pages 309-369
Brain Research Reviews

Full-length review
What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience?

https://doi.org/10.1016/S0165-0173(98)00019-8Get rights and content

Abstract

What roles do mesolimbic and neostriatal dopamine systems play in reward? Do they mediate the hedonic impact of rewarding stimuli? Do they mediate hedonic reward learning and associative prediction? Our review of the literature, together with results of a new study of residual reward capacity after dopamine depletion, indicates the answer to both questions is `no'. Rather, dopamine systems may mediate the incentive salience of rewards, modulating their motivational value in a manner separable from hedonia and reward learning. In a study of the consequences of dopamine loss, rats were depleted of dopamine in the nucleus accumbens and neostriatum by up to 99% using 6-hydroxydopamine. In a series of experiments, we applied the `taste reactivity' measure of affective reactions (gapes, etc.) to assess the capacity of dopamine-depleted rats for: 1) normal affect (hedonic and aversive reactions), 2) modulation of hedonic affect by associative learning (taste aversion conditioning), and 3) hedonic enhancement of affect by non-dopaminergic pharmacological manipulation of palatability (benzodiazepine administration). We found normal hedonic reaction patterns to sucrose vs. quinine, normal learning of new hedonic stimulus values (a change in palatability based on predictive relations), and normal pharmacological hedonic enhancement of palatability. We discuss these results in the context of hypotheses and data concerning the role of dopamine in reward. We review neurochemical, electrophysiological, and other behavioral evidence. We conclude that dopamine systems are not needed either to mediate the hedonic pleasure of reinforcers or to mediate predictive associations involved in hedonic reward learning. We conclude instead that dopamine may be more important to incentive salience attributions to the neural representations of reward-related stimuli. Incentive salience, we suggest, is a distinct component of motivation and reward. In other words, dopamine systems are necessary for `wanting' incentives, but not for `liking' them or for learning new `likes' and `dislikes'.

Introduction

Among the most thoroughly studied of all brain substrates for reward are dopamine projections from the substantia nigra and ventral tegmentum to forebrain structures such as the nucleus accumbens and neostriatum. It is generally recognized that mesolimbic and neostriatal dopamine projections are crucial to sensorimotor function, and so the sensorimotor consequences of dopamine manipulations complicate understanding the role of dopamine in reward 66, 202, 216, 286, 303, 378, 379, 381, 383, 391, 392, 456, 487. Nevertheless, many investigators have concluded that dopamine projections play a role in mediating the reward value of food, drink, sex, social reinforcers, drugs of abuse, and brain stimulation, above and beyond sensorimotor contributions 13, 17, 19, 26, 52, 115, 117, 145, 152, 155, 158, 225, 254, 259, 266, 268, 310, 325, 345, 347, 362, 363, 401, 423, 429, 505, 513, 518. The focus of this paper is on the nature of the contribution of mesolimbic and mesostriatal dopamine systems to reward.

Reward is often conceptualized as if it were a single psychological process or a unitary feature of a reinforcing stimulus. It is sometimes identified with the pleasure or hedonic impact of a stimulus, and is viewed by some as necessarily subjective in nature. We will argue that reward is not a unitary process, but instead a constellation of multiple processes many of which can be separately identified in behavior, especially after the component processes are dissociated by brain manipulations. Nor is reward a necessarily subjective event. Evidence for the proposition that reward and motivational processes are not necessarily subjective has been presented and reviewed elsewhere 34, 35, 161, 271, 273, 316, 366(for discussion see Berridge, in press [35]). Here we will be concerned solely with the separation of component processes of reward, and with the particular component mediated by dopamine-related brain systems.

Section snippets

Evidence for a role of dopamine in reward

Mesolimbic and neostriatal dopamine projections have been suggested to serve as a `common neural currency' for rewards of most kinds sought by animals and humans 268, 325, 347, 421, 505. Activation of dopamine systems, as quantified by electrophysiological, microdialysis, or voltammetric measures, is triggered in animals by encounters with food, sex, drugs of abuse, electrical stimulation at brain sites that support self-stimulation, and by secondary reinforcers for these incentives 5, 52, 159,

Brain manipulations of behavior for revealing dopamine's function in reward

The electrophysiological and neurochemical studies of dopamine activity discussed above do not allow us to conclusively exclude any hypothesis of dopamine function in reward. At best, these studies provide correlational evidence for a particular functional hypothesis, and at worst, the evidence is compatible with more than one hypothesis, perhaps with all. Thus, the results of electrophysiological and neurochemical studies so far do not by themselves justify rejection of the anhedonia

Effects of mesolimbic and neostriatal dopamine depletion on subcomponents of reward

This brings us to our current study, which was intended to deal with short-comings in our previous study, and to determine if any aspects of reward remain intact after the brain is depleted of mesolimbic and mesostriatal dopamine. First, several objections can be raised to our earlier conclusion that dopamine loss fails to produce anhedonia.

⋅ The average dopamine depletion in our earlier 6-OHDA study was only 85% [45]. Our animals were aphagic, but some have argued that dopamine depletion above

Surgery

Thirty-eight female and male Sprague–Dawley rats (260–310 g at surgery) were housed individually in plastic tub cages with wood shaving bedding.

Rats were anesthetized with ketamine (87 mg/kg. i.p.) and Rompun (13 mg/kg, i.p.). Each was pretreated with atropine methyl nitrate (5 mg/kg, i.p.) to prevent respiratory distress, bicillin (30,000 units, i.m.) to prevent infection, and desipramine (15 mg/kg, i.p.) and pargyline (50 mg/kg) to protect norepinephrine terminals and maximize dopamine

Subjects

Eight 6-OHDA lesion rats that remained aphagic 20 days after surgery but were otherwise in good health, and 7 control rats, were used in this Experiment. The 6-OHDA group included 7 rats that had >98% neostriatal dopamine depletion, and the 3 rats that had >99% depletion in both nucleus accumbens and neostriatum.

Taste CS+

A palatable and novel saccharin/polycose solution (0.2% w/v sodium saccharin and 32% w/v polycose) was used as the conditioned stimulus [408]. Polycose by itself does not taste sweet to

Experiment 3: enhancement of hedonic reaction patterns by diazepam

Experiment 2 demonstrated that dopamine depletion does not disrupt the capacity of learned negative associations to make tastes more aversive. But do 6-OHDA lesions eliminate the capacity to modulate palatability in the positive hedonic direction? Could hedonic reaction patterns still be enhanced? The conclusion that basic hedonic impact remains normal after dopamine depletion would be strengthened if that were true.

For normal rats hedonic reactions to taste are heightened by prior

General discussion

Are dopamine projections to the nucleus accumbens or neostriatum needed for normal hedonic evaluations, for hedonic modulation, or for learned adjustments in hedonic value? Our results indicate the answer to all three questions is `no'.

Dopamine and reward: choosing among competing explanations

Why do individuals fail to eat or drink voluntarily or show goal-directed behavior toward incentive stimuli after dopamine depletion? Competing hypotheses provide several different explanations. First, motor deficits produced by nigrostriatal impairment might render the animals incapable of the movements needed to eat or drink. Second, anhedonia caused by dopamine depletion might eliminate the hedonic impact of all food or drink reinforcers. Third, disruption of reward learning might make it

Conditioned dopamine activity: re-examination of implications for incentive salience and reward learning hypotheses

Our hypothesis predicts that neurons which mediate incentive salience will respond to sensory stimuli that trigger `wanting' regardless of whether they generate `liking'. As reviewed above, both dopamine neurons themselves and their neuronal targets in the striatum respond to incentive stimuli related to food or other rewards 3, 4, 5, 301, 305, 370, 403, 492. Although anticipatory neural responses in advance of a hedonic reward are usually discussed with a reward learning hypothesis in mind,

Comparing dopamine antagonist effects on hedonic activation

A primary conclusion of our review is that mesolimbic and neostriatal dopamine systems are not necessary for normal hedonic processes. It is reasonable to ask then, whether our conclusion can be reconciled with the wealth of evidence for anhedonia obtained over several decades. Nearly all the evidence for anhedonia came, as we pointed out above, from animal studies that involved either a measure of an instrumental behavior required to obtain a reward (bar pressing, running in a runway, etc.) or

Euphorigenic dopaminergic drugs

Probably the most convincing original evidence for the hedonia hypothesis, aside from animal studies of reward suppression by neuroleptic drugs, were demonstrations that most drugs of abuse promote activation of mesolimbic dopamine systems 266, 268, 505, 506, 507. Dopamine neurotransmission is generally enhanced by rewarding drugs, and many (though not all) addictive drugs of abuse produce subjective euphoria in humans. How can it be that so many drugs that enhance dopamine neurotransmission

Beyond reward to aversion

We would be remiss to end a discussion of the role of dopamine in reward without mention of its role in aversive motivational states such as fear or pain. There can be no doubt that behavior needed to actively avoid an unpleasant outcome is impaired as strongly by dopamine suppression as behavior directed toward a positive reward (for review, see Salamone [380]). The question is how involvement in aversive motivation bears on the role of dopamine in reward. For some investigators the

General conclusion

It is generally accepted that normal motivation and reward require the integrity of mesolimbic/mesostriatal dopamine systems. Some have interpreted the apparent primacy of dopamine systems to mean that these neutrons are a `common neural currency' for pleasant rewards, mediating the hedonic impact or pleasure of reinforcers. Others have instead posited dopamine systems to mediate reward learning or prediction. But our results and those reviewed above indicate that dopamine's role in reward is

Addendum 1: Taste reactivity patterns as a measure of `liking'

We do not mean to suggest that the subjective experience of pleasure is measured by the taste reactivity test. Instead, it measures a behavioral affective reaction 35, 109, 144, 273. A subjective experience need not even accompany a behavioral affective response (and almost certainly does not in some cases; for example, in the case of affective reaction patterns emitted by decerebrate animals or anencephalic human infants 211, 441). But hedonic and aversive patterns of affective reactions may

Addendum 2: Measuring cognitive expectations of reward in animals (studies of incentive learning by Dickinson and Balleine)

A cognitive expectation of reward is not merely elicitation of an affective or motivational response by a conditioned stimulus. It must also, Dickinson et al. 125, 126, 127suggest, be accompanied by the recognition by the animal that the to-be-obtained reward is obtained by its own action, and a representation of the to-be-obtained reward must be accessed to guide behavior to the goal. In other words, for an animal to have a cognitive expectation of a reward, it must know what reward it is

Note added in proof

An important review was published after this article went to press: W. Schultz, Predictive reward signals of dopamine neurons. J. Neurophysiol. 80 (1998) 1–27. In it, Schultz provides an excellent overview and adds substantial detail to the `reward learning' hypothesis of dopamine function. However, the theory remains similar in its essential points to that outlined in earlier reviews by Schultz and colleagues, and so we stand by our comments regarding the `dopamine reward learning' hypothesis.

Acknowledgements

Without implying acquiescence to the ideas presented here, we thank Drs. J. Wayne Aldridge, Steven Cooper, Howard (Casey) Cromwell, Anthony Dickinson, Susana Peciña, Per Södersten, Roland Suri, and Frederick Toates for helpful comments on earlier versions of this manuscript. We also thank Drs. Antoine Bechara, Karim Nader, and Derek van der Kooy for stimulating discussion of their reward hypothesis, and Gaetano Di Chiara for supplying an advance copy of a manuscript. Finally, we thank Dr. Diane

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