Kent C. Berridge

The debate over dopamine’s role in reward: the case for incentive salience

IntroductionDebate continues over the precise causal contribution made by mesolimbic dopamine systems to reward. There are three competing explanatory categories: ‘liking’, learning, and ‘wanting’. Does dopamine mostly mediate the hedonic impact of reward (‘liking’)? Does it instead mediate learned predictions of future reward, prediction error teaching signals and stamp in associative links (learning)? Or does dopamine motivate the pursuit of rewards by attributing incentive salience to reward-related stimuli (‘wanting’)? Each hypothesis is evaluated here, and it is suggested that the incentive salience or ‘wanting’ hypothesis of dopamine function may be consistent with more evidence than either learning or ‘liking’. In brief, recent evidence indicates that dopamine is neither necessary nor sufficient to mediate changes in hedonic ‘liking’ for sensory pleasures. Other recent evidence indicates that dopamine is not needed for new learning, and not sufficient to directly mediate learning by causing teaching or prediction signals. By contrast, growing evidence indicates that dopamine does contribute causally to incentive salience. Dopamine appears necessary for normal ‘wanting’, and dopamine activation can be sufficient to enhance cue-triggered incentive salience. Drugs of abuse that promote dopamine signals short circuit and sensitize dynamic mesolimbic mechanisms that evolved to attribute incentive salience to rewards. Such drugs interact with incentive salience integrations of Pavlovian associative information with physiological state signals. That interaction sets the stage to cause compulsive ‘wanting’ in addiction, but also provides opportunities for experiments to disentangle ‘wanting’, ‘liking’, and learning hypotheses. Results from studies that exploited those opportunities are described here.ConclusionIn short, dopamine’s contribution appears to be chiefly to cause ‘wanting’ for hedonic rewards, more than ‘liking’ or learning for those rewards.

The Neuroscience of Natural Rewards: Relevance to Addictive Drugs

Addictive drugs act on brain reward systems, although the brain evolved to respond not to drugs but to natural rewards, such as food and sex. Appropriate responses to natural rewards were evolutionarily important for survival, reproduction, and fitness. In a quirk of evolutionary fate, humans

The incentive sensitization theory of addiction: some current issues

We present a brief overview of the incentive sensitization theory of addiction. This posits that addiction is caused primarily by drug-induced sensitization in the brain mesocorticolimbic systems that attribute incentive salience to reward-associated stimuli. If rendered hypersensitive, these systems cause pathological incentive motivation (‘wanting’) for drugs. We address some current questions including: what is the role of learning in incentive sensitization and addiction? Does incentive sensitization occur in human addicts? Is the development of addiction-like behaviour in animals associated with sensitization? What is the best way to model addiction symptoms using animal models? And, finally, what are the roles of affective pleasure or withdrawal in addiction?

Affective neuroscience of pleasure: reward in humans and animals

IntroductionPleasure and reward are generated by brain circuits that are largely shared between humans and other animals.DiscussionHere, we survey some fundamental topics regarding pleasure mechanisms and explicitly compare humans and animals.ConclusionTopics surveyed include liking, wanting, and learning components of reward; brain coding versus brain causing of reward; subjective pleasure versus objective hedonic reactions; roles of orbitofrontal cortex and related cortex regions; subcortical hedonic hotspots for pleasure generation; reappraisals of dopamine and pleasure-electrode controversies; and the relation of pleasure to happiness.

Unconscious Affective Reactions to Masked Happy Versus Angry Faces Influence Consumption Behavior and Judgments of Value

The authors explored three properties of basic, unconsciously triggered affective reactions: They can influence consequential behavior, they work without eliciting conscious feelings, and they interact with motivation. The authors investigated these properties by testing the influence of subliminally presented happy versus angry faces on pouring and consumption of beverage (Study 1), perception of beverage value (Study 2), and reports of conscious feelings (both studies). Consistent with incentive motivation theory, the impact of affective primes on beverage value and consumption was strongest for thirsty participants. Subliminal smiles caused thirsty participants to pour and consume more beverage (Study 1) and increased their willingness to pay and their wanting more beverage (Study 2). Subliminal frowns had the opposite effect. No feeling changes were observed, even in thirsty participants. The results suggest that basic affective reactions can be unconscious and interact with incentive motivation to influence assessment of value and behavior toward valenced objects.

Hedonic Hot Spot in Nucleus Accumbens Shell: Where Do μ-Opioids Cause Increased Hedonic Impact of Sweetness?

μ-Opioid systems in the medial shell of the nucleus accumbens contribute to hedonic impact (“liking”) for sweetness, food, and drug rewards. But does the entire medial shell generate reward hedonic impact? Or is there a specific localized site for opioid enhancement of hedonic “liking” in the medial shell? And how does enhanced taste hedonic impact relate to opioid-stimulated increases in food intake? Here, we used a functional mapping procedure based on microinjection Fos plumes to localize opioid substrates in the medial shell of the nucleus accumbens that cause enhanced “liking” reactions to sweet pleasure and that stimulate food intake. We mapped changes in affective orofacial reactions of “liking”/“disliking” elicited by sucrose or quinine tastes after d-Ala2-N-Me-Phe4-Glycol5-enkephalin (DAMGO) microinjections in rats and compared hedonic increases to food intake stimulated at the same sites. Our maps indicate that opioid-induced increases in sucrose hedonic impact are generated by a localized cubic millimeter site in a rostrodorsal region of the medial shell. In contrast, all regions of the medial shell generated DAMGO-induced robust increases in eating behavior and food intake. Thus, our results identify a locus for opioid amplification of hedonic impact and reveal a distinction between opioid mechanisms of food intake and hedonic impact. Opioid circuits for stimulating food intake are widely distributed, whereas hedonic “liking” circuits are more tightly localized in the rostromedial shell of the nucleus accumbens.

Hedonic Hot Spots in the Brain

Hedonic “liking” for sensory pleasures is an important aspect of reward, and excessive ‘liking’ of particular rewards might contribute to excessive consumption and to disorders such as obesity. The present review aims to summarize recent advances in the identification of brain substrates for food ‘liking’ with a focus on opioid hot spots in the nucleus accumbens and ventral pallidum. Drug microinjection studies have shown that opioids in both areas amplify the ‘liking’ of sweet taste rewards. Modern neuroscience tools such as Fos plume mapping have further identified hedonic hot spots within the accumbens and pallidum, where opioids are especially tuned to magnify ‘liking’ of food rewards. Hedonic hot spots in different brain structures may interact with each other within the larger functional circuitry that interconnects them. Better understanding of how brain hedonic hot spots increase the positive affective impact of natural sensory pleasures will help characterize the neural mechanisms potentially involved in ‘liking’ for many rewards.

Pleasure Systems in the Brain

Pleasure is mediated by well-developed mesocorticolimbic circuitry and serves adaptive functions. In affective disorders, anhedonia (lack of pleasure) or dysphoria (negative affect) can result from breakdowns of that hedonic system. Human neuroimaging studies indicate that surprisingly similar circuitry is activated by quite diverse pleasures, suggesting a common neural currency shared by all. Wanting for reward is generated by a large and distributed brain system. Liking, or pleasure itself, is generated by a smaller set of hedonic hot spots within limbic circuitry. Those hot spots also can be embedded in broader anatomical patterns of valence organization, such as in a keyboard pattern of nucleus accumbens generators for desire versus dread. In contrast, some of the best known textbook candidates for pleasure generators, including classic pleasure electrodes and the mesolimbic dopamine system, may not generate pleasure after all. These emerging insights into brain pleasure mechanisms may eventually facilitate better treatments for affective disorders.

Towards a functional neuroanatomy of pleasure and happiness

The pursuit of happiness is a preoccupation for many people. Yet only the pursuit can be promised, not happiness itself. Can science help? We focus on the most tractable ingredient, hedonia or positive affect. A step toward happiness might be gained by improving the pleasures and positive moods in daily life. The neuroscience of pleasure and reward provides relevant insights, and we discuss how specific hedonic mechanisms might relate to happiness or the lack thereof. Although the neuroscience of happiness is still in its infancy, further advances might be made through mapping overlap between brain networks of hedonic pleasure with others, such as the brains default network, potentially involved in the other happiness ingredient, eudaimonia or life meaning and engagement.

Opioid Limbic Circuit for Reward: Interaction between Hedonic Hotspots of Nucleus Accumbens and Ventral Pallidum

μ-Opioid stimulation of cubic millimeter hedonic hotspots in either the nucleus accumbens shell (NAc) or the ventral pallidum (VP) amplifies hedonic “liking” reactions to sweetness and appetitive “wanting” for food reward. How do these two NAc–VP hotspots interact? To probe their interaction and limbic circuit properties, we assessed whether opioid activation of one hotspot recruited the other hotspot (neurobiologically) and whether opioid hedonic and incentive motivational amplification by either opioid hotspot required permissive opioid coactivation in the other (behaviorally). We found that NAc and VP hotspots reciprocally modulated Fos expression in each other and that the two hotspots were needed together to enhance sucrose “liking” reactions, essentially cooperating within a single hedonic NAc–VP circuit. In contrast, the NAc hotspot dominated for opioid stimulation of eating and food intake (“wanting”), independent of VP activation. This pattern reveals differences between limbic opioid circuits that control reward “liking” and “wanting” functions.