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

Abstract

Introduction

Debate 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.

Conclusion

In short, dopamine’s contribution appears to be chiefly to cause ‘wanting’ for hedonic rewards, more than ‘liking’ or learning for those rewards.

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Notes

  1. 1.

    Preliminary caveats

    Beyond dopamine caveat. In this paper, ‘the role of dopamine in reward’ is taken to be a short-hand term for the dopaminergic component of mesocorticolimbic systems. Dopamine is just one link in that chain of neuronal signals, and of course, we must go beyond dopamine neurons and synapses to understand reward function. Still, many causal manipulations powerfully affect reward by acting directly or indirectly on dopamine neurotransmission, and dopamine neural activation clearly codes reward events. Thus, dopamine deserves the special attention it has received as a crucial node of reward, and its precise role needs to be understood.

    Anatomical caveat. This discussion centers on mesolimbic dopamine projections especially to nucleus accumbens, but in practice, it is often difficult to distinguish the role of mesolimbic dopamine from neostriatal, cortical, and other dopamine systems. That is because many experiments use systemic drug administration, genetic manipulations or neural sensitization to alter reward, and all are bound to impact many dopamine systems simultaneously. Dopamine might well mediate different functions in different targets, even if involving similar cellular and molecular mechanisms in each structure, but the functional dividing lines between structures cannot yet be fully drawn. For that reason, I will de-emphasize specific anatomical targets here and attempt to consider dopamine’s most dominant role in reward. Still, we can, at least, surmise certain points about particular structures by a process of elimination. For example, if a reward function survives unchanged after dopamine is suppressed throughout the entire brain, then that function probably does not need dopamine in any particular brain structure.

    Tonic-phasic caveat. Similarly, phasic vs tonic dopamine signals might well have consequences that differ from each other, but we cannot tell them apart in most experiments that manipulate reward. So although the distinction’s importance is not denied, I will mostly focus on what we can say about the role of dopamine in reward more generally without trying to assign causal responsibility specifically to phasic or tonic signals.

  2. 2.

    ‘Reinforcing’ terminology is slightly ambiguous: ‘Reinforcement’ often means the positive affective value or hedonic impact of a reward stimulus, as when applied to the hedonia hypothesis. It was long used as a technical term for hedonic impact, and some neuroscientists still use positive reinforcement as their chief synonym for positive affect or emotion today (Rolls 2005). Alternatively, reinforcement can sometimes mean a purely associative strengthening of learned S–S or S–R links without any affective connotations. Yet, a third meaning is radical behaviorist, where it refers simply to an observed strengthening of prior responses on which the reinforcer is contingent, with no explanatory connotations at all of underlying neural or psychological mechanisms. In any case, reinforcement was often used in a hedonic sense by many dopamine-reward papers in the 1980s–1990s and apparently in the hedonia quotes mentioned above.

  3. 3.

    Even in ordinary people, purely objective or non-subjective affective reactions can be demonstrated under certain conditions in the form of unconscious ‘liking’. For example, a subliminal happy or fearful facial expression, viewed too briefly to be consciously perceived, can produce affective reactions that markedly change a person’s subsequent affective rating and consumption of a subsequent hedonic stimulus (sweet beverage), without ever being felt at the moment the hedonic reaction was caused (Berridge and Winkielman 2003; Winkielman et al. 2005). To become subjectively felt, such ‘unconscious liking’ reactions may require further brain processing, presumably including orbitofrontal and related cortical mechanisms (Kringelbach 2005). But the point here is that if ‘unconscious liking’ reactions ever exist at all, then it means that objective indicators of hedonic reactions can sometimes reveal more about underlying pleasure mechanisms than verbal reports, even in people.

    The probable homology of taste ‘liking’ reactions in humans and rats is indicated by several observations. For example, microfeatures of taste reactivity patterns show taxonomic clustering across species: humans share the greatest number of reaction details with other hominids (great apes such as orangutans and chimpanzees), share moderately with old world monkeys and new world monkeys (which cluster into their own groups), and share lightly with rodents (rats and mice; also cluster together) (Berridge 2000; Steiner et al. 2001). But all primates and rodent species tested so far share at least a half dozen reaction details all in common (e.g., rhythmic tongue protrusions to sweet tastes and negative ‘disliking’ gapes to bitter tastes). The homology of those shared components is further indicated by the fact that those shared components also share the same identical rule for generating certain aspects of expression microstructure, such as allometric timing, in primates (including humans) and rodents alike. For example, the duration of expression components observes the equation:

    $${\text{duration}}{\left( {{\text{in}}\,{\text{ms}}} \right)} = 0.26 \times {\left( {{\text{adult}}\,{\text{species}}\,{\text{weight}}\,{\left[ {{\text{in}}\,{\text{kg}}} \right]}} \right)}^{{0.32}} $$

    That allometry rule means that the human or gorilla tongue protrusion or gape is relatively slow, whereas, the same reaction in a rat or mouse reaction is much faster, yet all have identical timing ‘deep structure’ scaled to their evolved size. Finally, other observations indicate that those timing rules for ‘liking’ and ‘disliking’ reactions for each species are actively programmed by brain circuits For example, infants and adults share the same species timing, despite their different sizes, which further indicates homology of brain mechanisms and that timing is not passively produced by actual size acting on the physics of movement (Berridge 2000; Steiner et al. 2001). The implication of the probable homology of taste ‘liking’ reactions for affective neuroscience studies of hedonic impact is that identification of hedonic hotspots and neurochemical bases of ‘liking’ in rats can provide insights that probably apply also to brain hedonic mechanisms in humans.

    Several demonstrations reveal that hedonic neural hierarchies control the expression of ‘liking’ reactions used in our taste reactivity studies. For example, microinjections of opioid agonists and other neurotransmitter agents in forebrain structures such as the nucleus accumbens and ventral pallidum cause increases in ‘liking’ reactions, whereas, forebrain lesions of the ventral pallidum or ‘thalamic’ ablation of telencephalon cause increases in ‘disliking’ reactions (Cromwell and Berridge 1993; Grill and Norgren 1978b; Peciña and Berridge 2000, 2005; Reynolds and Berridge 2002; Smith and Berridge 2005). Taste reactivity ‘liking’ patterns have also been used to guide positive identification of neural firing patterns in the forebrain that code hedonic impact (e.g., rate codes by neurons in ventral pallidum) (Tindell et al. 2006). Such forebrain-related observations extend traditional notions of taste reactivity as a brainstem response, which were grounded on basic taste reactions elicited from decerebrate rats or cats or from anencephalic humans (Grill and Norgren 1978b; Sherrington 1906; Steiner 1973), by demonstrating that forebrain hedonic circuits normally exert overriding dominance over brainstem circuits in the control of ‘liking’ reactions, and that forebrain hedonic signals are normally reflected in behavioral ‘liking’ reactions.

  4. 4.

    In fact, many of the dopamine activations described that caused ‘wanting’-without-‘liking’ in our taste reactivity studies slightly reduced the number of ‘liking’ reactions to sweet taste while simultaneously stimulating ‘wanting’ for food reward, a potential hedonic suppression that is opposite from what the hedonia hypothesis should predict (dopamine-mediated suppression of ‘liking’ appears to be independent of incentive salience attribution; the mechanism of hedonic suppression is not fully understood but might conceivably involve interaction with known opioid or gamma-aminobutyric acid (GABA) hedonic mechanisms in nucleus accumbens).

  5. 5.

    Direct vs indirect roles in learning: Clear evidence for indirect roles of dopamine

    It can be useful to distinguish between potential direct causal roles of dopamine, as part of an associative mechanism that learns associative links between S–S or S–R events (teaching signal δ(t), engram stamping-in, prediction V), and indirect roles on other extrinsic mechanisms separate from learning that feed back secondarily to modulate learning or later use of learned information.

    Dopamine and other catecholamine activation may facilitate the capacity to extract new information from training trials, facilitate consolidation after learning, and facilitate learned performance later. For example, dopamine manipulations before training can modulate learning features such as latent inhibition for reward or fear CSs (Gray et al. 1999; Phillips et al. 2003a; Schmajuk et al. 2001), dopamine agonists given before performance tests enhance the motivational value of CSs in conditioned reinforcement and other tasks (and the enhancement can be blocked by accumbens 6-OHDA lesions) (Robbins and Everitt 1996; Taylor and Robbins 1984, 1986). In addition, elegant recent studies have demonstrated that dopamine may contribute to consolidation processes that continue for many minutes after a S–S or S–R learning trial has ended and that help make an already learned association more readily available for later use (Dalley et al. 2005). These consolidation effects appear related to the consolidation effects that have been well documented for norepinephrine, stress hormones, and certain other neurochemical modulators (Dalley et al. 2005; Everitt and Robbins 2005; McGaugh 2002; Smith-Roe and Kelley 2000). Thus, dopamine may indirectly affect the extraction of information from environments or the later use of learned information in many ways. Those roles may remain, even if dopamine in not the primary teaching signal that directly causes new learning.

  6. 6.

    Why do addicts ‘want’ just drugs? An extension of salience specificity

    Dopamine drugs that activate mesolimbic systems short circuit normal physiological-learning interaction, by plugging directly into the neurobiological mechanism that ordinarily adjusts learned incentive salience in accordance with physiological states. Drugs that activate dopamine neurotransmission or induce neural sensitization may thus directly elevate ‘wanting’ for rewards in a manner that will still be cue-sensitive and reward-specific. Similarly, more enduring effects of addictive drugs, such as neural sensitization, may permanently elevate mesolimbic neural responsiveness to certain motivational stimuli, and increase incentive salience or ‘wanting’ for those rewards, especially drug rewards. This is the basis for the incentive-sensitization theory of addiction, the development of which was led by my colleague Terry Robinson (Robinson and Berridge 1993). It combines the incentive salience hypothesis of what dopamine-related mesolimbic systems contribute to reward with the idea that drugs of abuse may sensitize the same mesolimbic systems in susceptible human addicts.

    It is sometimes objected that incentive-sensitization could not possibly be specific enough to make drugs ‘wanted’ more than other stimuli. For example, Vanderschuren and Everitt engagingly proposed that “incentive sensitization caused by repeated drug exposure can explain the exaggerated motivation for drugs associated with addiction, but not the fact that drug-related activities prevail at the expense of previously important social and professional activities” (Vanderschuren and Everitt 2005). That proposal seems to suppose that incentive-sensitization must necessarily make all things equally more ‘wanted’: drugs and social or professional success alike, similar to the adage that ‘a rising tide floats all boats’. But recent evidence indicates that it is probably more accurate to say that sensitization amplifies ‘wanting’ in ways that can be quite specific to one motivational target rather than another. For example, sensitization may make drugs more ‘wanted’ than natural rewards for some individuals but for others make food or sex more ‘wanted’ than drug (Nocjar and Panksepp 2002). In other experiments described under incentive salience, sensitization can more than triple the ability of some particular cues to trigger ‘wanting’ for their reward, while leaving other cues and baseline motivation in the absence of cues, essentially unchanged (e.g., CS+2 vs CS+1 for incentive coding by ventral pallidum neuronal firing; CS+ vs CS− for behavioral cue-triggered ‘wanting’ in PIT (Tindell et al. 2005; Wyvell and Berridge 2001). Thus, incentive-sensitization can often enhance ‘wants’ for some rewards much more than other rewards, and at some moments, much more than other moments.

    Still, in accordance with Vanderschuren and Everitt’s proposal of broad motivational ‘wanting’, sensitized incentive salience can sometimes spillover, too, in humans and animals at least under some conditions. For example, Fiorino and Phillips observed that “As many as 70% of patients admitted to a New York cocaine addiction treatment program were also reported to suffer from compulsive sexuality” in a study showing that amphetamine sensitization also amplified sexual behavior and dopamine release in rats (Fiorino and Phillips 1999; Washton and Stone-Washton 1993). Parkinson’s patients with dopamine dysregulation who become addicted to over-consuming l-DOPA, may also show other motivational compulsions including gambling, sexual behavior, and obsessive desire to repeat trivial pursuits like sorting drawers (punding) (Dodd et al. 2005; Evans et al. 2006). But even in such cases, some motivational targets are ‘wanted’ much more than others. Thus, target specificity, more than generality, probably is the guiding rule for dopamine-enhanced ‘wanting’, and there might even be cases where ‘winner takes all’.

    In addiction, drugs might be specifically enhanced as targets for sensitization of incentive salience because they have a privileged Bindra–Toates associative relationship as UCS to predictive drug-related CSs, in addition to being strong stimuli for activating and sensitizing dopamine systems directly. In short, activating mesolimbic systems by dopamine agonist drug or by sensitization may amplify and distort the normal specificity by which some stimuli become ‘wanted’ much more than others, but the specificity is not abolished. That may be why addicts ‘want’ their drugs more than other rewards or social success.

  7. 7.

    The test situation occurred too soon—that is, before new relearning of dopamine-augmented reward value was possible—for any existing prediction error model to produce an increment in CS-triggered V, the associative prediction of future reward, in the studies of Tindell et al. (2005) or Wyvell and Berridge (2000, 2001). V increments require retraining with an elevated UCS teaching signal. Because mesolimbic activation (sensitization and/or acute amphetamine) was delayed until after training finished, there were no opportunities for prediction error to enhance a teaching signal for V before the first test trial (even if dopamine activation had increased the prediction error UCS signal). Thus, V could not possibly have been enhanced on the first test trial without doing serious violence to the right side of the V equation of the temporal difference model. However, conceivably future computational learning models will escape the ‘need-another-UCS-experience’ constraint of cache-based models and become better able to cope with sudden shifts in value that are not gradually relearned. For example, recent tree-search models have been proposed that exhaustively examine all potential outcomes, pulling up each one for a thorough reevaluation of its utility values—but only so far applied to cortex function and explicitly not to mesolimbic dopamine function (Daw et al. 2005). Still, perhaps a related future model, if applied to mesolimbic dopamine function, might be able to allow ‘instant increases’ in CS predicted utility produced by post-learning sensitization or drug administration. Even if so, though, such future ‘prescient-V-increment’ models still will encounter a major obstacle in the finding by that dopamine activation enhanced the strength of the CS incentive code (CS+2) at the expense of the CS prediction V code strength (CS+1) in the computational profile analysis of neuronal coding in ventral pallidum in Tindell et al. (2005).

  8. 8.

    Remaining difficulties with the incentive salience hypothesis. Many readers may have noted explanatory gaps that were skipped over in the section above. Though it means momentarily stepping aside from my debate mission here, my colleagues and I readily acknowledge that incentive salience is by no means a complete theory, but only an interim and skeletal hypothesis of dopamine and mesocorticolimbic function that needs additional development on many points. It is based on data available to date, but that is incomplete on several points. The gaps are real and need to be plugged by further research.

    For example, one gap needing attention concerns the relative roles of stage 2 reboosting and stage 3 dynamic generation of incentive salience attributions to a CS. Reboosting is the one feature of the incentive salience hypothesis that was added as a purely post hoc postulate to explain hedonia-type dopamine phenomena from other laboratories. It was added purely to explain why dopamine antagonist drugs sometimes produced what looked like anhedonia effects on instrumental reward tasks, such as the ‘extinction mimicry’ effects described by Wise and others (Ettenberg and McFarland 2003; Wise 1985, 2004a; though compare Salamone et al. 1997). My colleagues and I were quite familiar with extinction mimicry reports by the late 1980s. Indeed, I had been convinced by them that dopamine did mediate hedonic impact, at least, until we began to find ourselves that basic hedonic ‘liking’ reactions were not at all suppressed by dopamine reduction. We devised reboosting as a postulate specifically to reconcile extinction mimicry effects with preserved hedonic impact, in an effort to explain why dopamine could look as though it mediated pleasure when it actually did not (Berridge and Valenstein 1991; Robinson and Berridge 1993).

    As a consequence, reboosting is an add-on feature, somewhat messy though still quite necessary. It operates to influence incentive salience attributions to CSs during pairing with UCSs in stage 2, in addition to the stage 3 integration of prior UCS value and relevant physiological state that occurs when the CS is next encountered. But this degree of messiness may be an acceptable theoretical price that must be paid to buy the most data. In addition, reboosting might prove important in explaining some cases of resistance to goal devaluation, cases in which a reward CS remains ‘wanted’ even after its UCS goal is suddenly devalued and becomes no longer attractive (e.g., by pairing UCS food reward with LiCl illness). In those cases, the incentive salience of the CS may become independent of its UCS, so the CS may be no longer dynamically adjusted in stage 3 based strictly on current UCS value (perhaps persisting especially when additional associative layers such as aversion conditioning or sensory-specific habituation, rather than a direct physiological state shift such as hunger, are used to revalue the UCS). One possible explanation is that repeated reboosting of incentive salience to CS, before the devaluation, sometimes builds up ‘wanting’ for the cue in a way that to some degree becomes independent from stage 3 integration with the current state. In that case, the CS might remain attractive even after the UCS incentive value is gone. Of course, this account of resistance to devaluation is purely speculative, but it could be evaluated empirically that the relation between stage 2 reboosting and stage 3 dynamic integration become clarified by future results. To sum up reboosting, the evidence available suggests that dopamine influences incentive salience both via reboosting (during UCS training) and via dynamic mesolimbic generation (later at moment of CS reexposure). Both routes can be modeled computationally and studied experimentally. Together, they may cover much of the dopamine-related evidence on reward that gave rise originally to hedonia and stamping-in reinforcement hypotheses and motivation ‘wanting’ effects.

    Another difficulty that needs addressing in the future is to develop a more complete account of how dopamine effects on CS incentive salience are translated into UCS-directed instrumental actions beyond simple approach behaviors. The puzzle to be explained is how incentive salience becomes attributed to reward representation targets of instrumental responses or even sometimes to instrumental acts themselves. The evidence shows it does. One clear example is cue-triggered ‘wanting’ based on Pavlovian-instrumental transfer (chosen because it strips away alternative explanations) (Dickinson et al. 2000; Peciña et al. 2006; Wyvell and Berridge 2000, 2001). Cue-triggered ‘wanting’ is arguably potent in many human situations, such as addictive cue-triggered relapse. Instrumental application of incentive salience might also contribute to conditioned instrumental reinforcement situations, where individual work simply to gain a reward cue. Dopamine activation potently magnifies conditioned reinforcement (Everitt et al. 1999; Everitt and Robbins 2005). In such cases, animals must use a central neural representation of the CS incentive to guide their action because the physical cue does not occur until after the action (though contextual cues likely serve as occasion setters to activate the cue representation and incentive salience attribution). A similar logic might also apply the role of cues in seeking–taking situations or cases where earning a cue (in addition to drug reward) contributes an increment to motivation for earning the unconditioned reward by itself (Nicola et al. 2005; Vanderschuren and Everitt 2005). But a good theoretical account of how incentive salience is attributed by dopamine-related mechanisms precisely to motivate instrumental actions will need future work (Dickinson and Balleine 2002).

    An additional difficulty is how to reconcile the apparent failure of dopamine to directly cause learning with other evidence that dopamine indirectly modulates learning. As noted above, numerous studies have indicated a role for dopamine neurotransmission in modulating cellular plasticity (e.g., long-term potentiation) and in memory consolidation after learning and modulating attention and other functions that act during training and during test performance based on learned information (Dalley et al. 2005; Everitt and Robbins 2005; McGaugh 2002; Smith-Roe and Kelley 2000). Yet at the same time, recent evidence suggests that dopamine is not serving as a prediction error δ(t) to stamp-in new S–S or S–R associations or to generate learned predictions as V (e.g., ability of mutant mice to learn without dopamine; merely normal learning in other mutant mice with excessive dopamine; failure of dopamine activation to elevate limbic neural coded signal for learning δ(t) or V in recorded mesolimbic outputs in ventral pallidum). Clearly, it is of great importance to understand better exactly what dopamine does to indirectly modulate learning-related mechanisms.

    There are other deficiencies too: for example, there is a pressing need for computational models that better capture dynamic integrative features of incentive salience described above (Zhang et al. 2005). But these difficulties generally seem to be challenges that can be reasonably expected to be met in time and are not insurmountable obstructions. Most important, to return to the central theme of dopamine function, the incentive salience hypothesis is sufficiently developed at present that it can be empirically tested, as in experiments above. It makes specific predictions that can be quite feasibly pitted against learning and ‘liking’ hypotheses of dopamine function in reward. In the cases above where that has been done, the data, so far, support the hypothesis that dopamine causes ‘wanting’ more directly than either learning or ‘liking’ for reward.

References

  1. Ahn S, Phillips AG (1999) Dopaminergic correlates of sensory-specific satiety in the medial prefrontal cortex and nucleus accumbens of the rat. J Neurosci 19:B1–B6

    Google Scholar 

  2. Ainslie G (1992) Picoeconomics. Cambridge University Press, Cambridge University Press

  3. Albin RL, Young AB, Penney JB (1995) The functional anatomy of disorders of the basal ganglia. Trends Neurosci 18:63–64

    PubMed  CAS  Google Scholar 

  4. Andrzejewski ME, Spencer RC, Kelley AE (2005) Instrumental learning, but not performance, requires dopamine D1-receptor activation in the amygdala. Neuroscience 135:335–345

    PubMed  CAS  Google Scholar 

  5. Aragona BJ, Liu Y, Yu YJ, Curtis JT, Detwiler JM, Insel TR, Wang Z (2006) Nucleus accumbens dopamine differentially mediates the formation and maintenance of monogamous pair bonds. Nat Neurosci 9:133–139

    PubMed  CAS  Google Scholar 

  6. Baldo BA, Daniel RA, Berridge CW, Kelley AE (2003) Overlapping distributions of orexin/hypocretin- and dopamine-beta-hydroxylase immunoreactive fibers in rat brain regions mediating arousal, motivation, and stress. J Comp Neurol 464:220–237

    PubMed  Google Scholar 

  7. Baldwin AE, Sadeghian K, Holahan MR, Kelley AE (2002) Appetitive instrumental learning is impaired by inhibition of cAMP-dependent protein kinase within the nucleus accumbens. Neurobiol Learn Mem 77:44–62

    PubMed  CAS  Google Scholar 

  8. Bayer HM, Glimcher PW (2005) Midbrain dopamine neurons encode a quantitative reward prediction error signal. Neuron 47:129–141

    PubMed  CAS  Google Scholar 

  9. Becker JB, Rudick CN, Jenkins WJ (2001) The role of dopamine in the nucleus accumbens and striatum during sexual behavior in the female rat. J Neurosci 21:3236–3241

    PubMed  CAS  Google Scholar 

  10. Berke JD (2003) Learning and memory mechanisms involved in compulsive drug use and relapse. In: Wang JQ (ed) Drugs of abuse: neurological reviews and protocols (Methods in Molecular Medicine). Humana, Totowa, NJ, pp 75–101

    Google Scholar 

  11. Berke JD, Hyman SE (2000) Addiction, dopamine, and the molecular mechanisms of memory. Neuron 25:515–532

    PubMed  CAS  Google Scholar 

  12. Berridge KC (2000) Measuring hedonic impact in animals and infants: microstructure of affective taste reactivity patterns. Neurosci Biobehav Rev 24:173–198

    PubMed  CAS  Google Scholar 

  13. Berridge KC (2001) Reward learning: reinforcement, incentives, and expectations. In: Medin DL (ed) The psychology of learning and motivation. Academic, NY, pp 223–278

    Google Scholar 

  14. Berridge KC (2004) Motivation concepts in behavioral neuroscience. Physiol Behav 81:179–209

    PubMed  CAS  Google Scholar 

  15. Berridge KC, Peciña S (1995) Benzodiazepines, appetite, and taste palatability. Neurosci Biobehav Rev 19:121–131

    PubMed  CAS  Google Scholar 

  16. Berridge KC, Robinson TE (1998) What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience? Brain Res Rev 28:309–369

    PubMed  CAS  Google Scholar 

  17. Berridge KC, Schulkin J (1989) Palatability shift of a salt-associated incentive during sodium depletion. Q J Exp Psychol [b] 41:121–138

    CAS  Google Scholar 

  18. Berridge KC, Valenstein ES (1991) What psychological process mediates feeding evoked by electrical stimulation of the lateral hypothalamus? Behav Neurosci. 105:3–14

    PubMed  CAS  Google Scholar 

  19. Berridge KC, Winkielman P (2003) What is an unconscious emotion? (The case for unconscious “liking”). Cogn Emot 17:181–211

    Google Scholar 

  20. Berridge KC, Venier IL, Robinson TE (1989) Taste reactivity analysis of 6-hydroxydopamine-induced aphagia: implications for arousal and anhedonia hypotheses of dopamine function. Behav Neurosci 103:36–45

    PubMed  CAS  Google Scholar 

  21. Berridge KC, Aldridge JW, Houchard KR, Zhuang X (2005) Sequential super-stereotypy of an instinctive fixed action pattern in hyper-dopaminergic mutant mice: a model of obsessive compulsive disorder and Tourette’s. BMC Biol 3:4

    PubMed  Google Scholar 

  22. Bindra D (1978) How adaptive behavior is produced: a perceptual-motivation alternative to response reinforcement. Behav Brain Sci 1:41–91

    Google Scholar 

  23. Bolles RC (1972) Reinforcement, expectancy, & learning. Psychol Rev 79:394–409

    Google Scholar 

  24. Brauer LH, De Wit H (1997) High dose pimozide does not block amphetamine-induced euphoria in normal volunteers. Pharmacol Biochem Behav 56:265–272

    PubMed  CAS  Google Scholar 

  25. Brauer LH, Rukstalis MR, de Wit H (1995) Acute subjective responses to paroxetine in normal volunteers. Drug Alcohol Depend 39:223–230

    PubMed  CAS  Google Scholar 

  26. Brauer LH, Goudie AJ, de Wit H (1997) Dopamine ligands and the stimulus effects of amphetamine: animal models versus human laboratory data. Psychopharmacology (Berl) 130:2–13

    CAS  Google Scholar 

  27. Brauer LH, Cramblett MJ, Paxton DA, Rose JE (2001) Haloperidol reduces smoking of both nicotine-containing and denicotinized cigarettes. Psychopharmacology (Berl) 159:31–37

    CAS  Google Scholar 

  28. Cabanac M (1979) Sensory pleasure. Q Rev Biol 54:1–29

    PubMed  CAS  Google Scholar 

  29. Cabanac M (1992) Pleasure: the common currency. J Theor Biol 155:173–200

    PubMed  CAS  Google Scholar 

  30. Cagniard B, Balsam PD, Brunner D, Zhuang X (2005) Mice with chronically elevated dopamine exhibit enhanced motivation, but not learning, for a food reward. Neuropsychopharmacology 31(7):1362–1370

    PubMed  Google Scholar 

  31. Cannon CM, Bseikri MR (2004) Is dopamine required for natural reward? Physiol Behav 81:741–748

    PubMed  CAS  Google Scholar 

  32. Cannon CM, Palmiter RD (2003) Reward without dopamine. J Neurosci 23:10827–10831

    PubMed  CAS  Google Scholar 

  33. Carelli RM (2004) Nucleus accumbens cell firing and rapid dopamine signaling during goal-directed behaviors in rats. Neuropharmacology 47 Suppl 1:180–189

    PubMed  CAS  Google Scholar 

  34. Cooper SJ, Dourish CT (1990) Neurobiology of stereotyped behaviour. Oxford University Press, Oxford University Press

  35. Corbit LH, Balleine BW (2003) Instrumental and Pavlovian incentive processes have dissociable effects on components of a heterogeneous instrumental chain. J Exp Psychol Anim Behav Processes 29:99–106

    Google Scholar 

  36. Cromwell HC, Berridge KC (1993) Where does damage lead to enhanced food aversion: the ventral pallidum/substantia innominata or lateral hypothalamus? Brain Res 624:1–10

    PubMed  CAS  Google Scholar 

  37. Cromwell HC, Berridge KC (1996) Implementation of action sequences by a neostriatal site: A lesion mapping study of grooming syntax. J Neurosci 16:3444–3458

    PubMed  CAS  Google Scholar 

  38. Cromwell HC, Schultz W (2003) Effects of expectations for different reward magnitudes on neuronal activity in primate striatum. J Neurophysiol

  39. Cromwell HC, Hassani OK, Schultz W (2005) Relative reward processing in primate striatum. Exp Brain Res 162:520–525

    PubMed  Google Scholar 

  40. Crow TJ (1973) Catecholamine-containing neurones and electrical self-stimulation. 2. A theoretical interpretation and some psychiatric implications. Psychol Med 3:66–73

    PubMed  CAS  Article  Google Scholar 

  41. Dalley JW, Laane K, Theobald DEH, Armstrong HC, Corlett PR, Chudasama Y, Robbins TW (2005) Time-limited modulation of appetitive Pavlovian memory by D1 and NMDA receptors in the nucleus accumbens. PNAS 102:6189–6194

    PubMed  CAS  Google Scholar 

  42. Damasio AR (1999) The feeling of what happens: body and emotion in the making of consciousness, 1st edn. Harcourt Brace, Harcourt Brace

  43. Darwin C (1872) The expression of the emotions in man and animals. Murray, London

    Google Scholar 

  44. Dauer W, Przedborski S (2003) Parkinson’s disease: mechanisms and models. Neuron 39:889–909

    PubMed  CAS  Google Scholar 

  45. Daw ND, Niv Y, Dayan P (2005) Uncertainty-based competition between prefrontal and dorsolateral striatal systems for behavioral control. Nature Neurosci 8:1704–1711

    PubMed  CAS  Google Scholar 

  46. Day JJ, Wheeler RA, Roitman MF, Carelli RM (2006) Nucleus accumbens neurons encode Pavlovian approach behaviors: evidence from an autoshaping paradigm. Eur J Neurosci 23:1341–1351

    PubMed  Google Scholar 

  47. Dayan P, Balleine BW (2002) Reward, motivation, and reinforcement learning. Neuron 36:285–298

    PubMed  CAS  Google Scholar 

  48. de la Fuente-Fernandez R, Phillips AG, Zamburlini M, Sossi V, Calne DB, Ruth TJ, Stoessl AJ (2002) Dopamine release in human ventral striatum and expectation of reward. Behav Brain Res 136:359–363

    PubMed  Google Scholar 

  49. Deroche V, Le Moal M, Piazza PV (1999) Cocaine self-administration increases the incentive motivational properties of the drug in rats. Eur J Neurosci 11:2731–2736

    PubMed  CAS  Google Scholar 

  50. Deveney AM, Waddington JL (1997) Psychopharmacological distinction between novel full-efficacy “D-1-like” dopamine receptor agonists. Pharmacol Biochem Behav 58:551–558

    PubMed  CAS  Google Scholar 

  51. Di Chiara G (2002) Nucleus accumbens shell and core dopamine: differential role in behavior and addiction. Behav Brain Res 137:75–114

    PubMed  Google Scholar 

  52. Di Ciano P, Underwood RJ, Hagan JJ, Everitt BJ (2003) Attenuation of cue-controlled cocaine-seeking by a selective D-3 dopamine receptor antagonist SB-277011-A. Neuropsychopharmacology 28:329–338

    PubMed  Google Scholar 

  53. Diaz-Mataix L, Artigas F, Celada P (2006) Activation of pyramidal cells in rat medial prefrontal cortex projecting to ventral tegmental area by a 5-HT1A receptor agonist. Eur Neuropsychopharmacol 16:288–296

    PubMed  CAS  Google Scholar 

  54. Dickinson A, Balleine B (2002) The role of learning in the operation of motivational systems. In: Gallistel CR (ed) Stevens’ handbook of experimental psychology: learning, motivation, and emotion. Wiley, New York, pp 497–534

    Google Scholar 

  55. Dickinson A, Smith J, Mirenowicz J (2000) Dissociation of Pavlovian and instrumental incentive learning under dopamine antagonists. Behav Neurosci 114:468–483

    PubMed  CAS  Google Scholar 

  56. Dodd ML, Klos KJ, Bower JH, Geda YE, Josephs KA, Ahlskog JE (2005) Pathological gambling caused by drugs used to treat Parkinson disease. Arch Neurol 62(9):1377–1381

    PubMed  Google Scholar 

  57. Dommett E, Coizet V, Blaha CD, Martindale J, Lefebvre V, Walton N, Mayhew JE, Overton PG, Redgrave P (2005) How visual stimuli activate dopaminergic neurons at short latency. Science 307:1476–1479

    PubMed  CAS  Google Scholar 

  58. Ekman P (1999) Basic emotions handbook of cognition and emotion. Wiley, Chichester, England, pp 45–60

    Google Scholar 

  59. Elliott R, Newman JL, Longe OA, Deakin JFW (2003) Differential response patterns in the striatum and orbitofrontal cortex to financial reward in humans: a parametric functional magnetic resonance imaging study. J Neurosci 23:303–307

    PubMed  CAS  Google Scholar 

  60. Ettenberg A, McFarland K (2003) Effects of haloperidol on cue-induced autonomic and behavioral indices of heroin reward and motivation. Psychopharmacology (Berl) 168:139–145

    CAS  Google Scholar 

  61. Evans AH, Pavese N, Lawrence AD, Tai YF, Appel S, Doder M, Brooks DJ, Lees AJ, Piccini P (2006) Compulsive drug use linked to sensitized ventral striatal dopamine transmission. Ann Neurol 59:852–858

    PubMed  CAS  Google Scholar 

  62. Everitt BJ, Robbins TW (2005) Neural systems of reinforcement for drug addiction: from actions to habits to compulsion. Nat Neurosci 8:1481–1489

    PubMed  CAS  Google Scholar 

  63. Everitt BJ, Parkinson JA, Olmstead MC, Arroyo M, Robledo P, Robbins TW (1999) Associative processes in addiction and reward. The role of amygdala–ventral striatal subsystems. Ann N Y Acad Sci 877:412–438

    PubMed  CAS  Google Scholar 

  64. Everitt BJ, Dickinson A, Robbins TW (2001) The neuropsychological basis of addictive behaviour. Brain Res Rev 36:129–138

    PubMed  CAS  Google Scholar 

  65. Faure A, Haberland U, Conde F, Massioui NE (2005) Lesion to the nigrostriatal dopamine system disrupts stimulus-response habit formation. J Neurosci 25:2771–2780

    PubMed  CAS  Google Scholar 

  66. Fenu S, Di Chiara G (2003) Facilitation of conditioned taste aversion learning by systemic amphetamine: role of nucleus accumbens shell dopamine D-1 receptors. Eur J Neurosci 18: 2025–2030

    PubMed  Google Scholar 

  67. Ferraro FM 3rd, Hill KG, Kaczmarek HJ, Coonfield DL, Kiefer SW (2002) Naltrexone modifies the palatability of basic tastes and alcohol in outbred male rats. Alcohol 27:107–114

    PubMed  CAS  Google Scholar 

  68. Fibiger HC, Phillips AG (1986) Reward, motivation, cognition: Psychobiology of mesotelencephalic systems. In: Bloom FE (ed) Handbook of Physiology—The Nervous System. American Physiological Society, Bethesda, MD. pp 647–675

    Google Scholar 

  69. Fiorino DF, Phillips AG (1999) Facilitation of sexual behavior and enhanced dopamine efflux in the nucleus accumbens of male rats after d-amphetamine-induced behavioral sensitization. J Neurosci 19:456–463

    PubMed  CAS  Google Scholar 

  70. Fiorino DF, Coury A, Phillips AG (1997) Dynamic changes in nucleus accumbens dopamine efflux during the Coolidge effect in male rats. J Neurosci 17:4849–4855

    PubMed  CAS  Google Scholar 

  71. Fudim OK (1978) Sensory preconditioning of flavors with a formalin-produced sodium need. J Exp Psychol Anim Behav Process 4:276–285

    PubMed  CAS  Google Scholar 

  72. Fulton S, Woodside B, Shizgal P (2000) Modulation of brain reward circuitry by leptin [published erratum appears in Science 2000 Mar 17;287(5460):1931]. Science 287:125–128

    PubMed  CAS  Google Scholar 

  73. Gallistel CR, Fairhurst S, Balsam P (2004) The learning curve: implications of a quantitative analysis. Proc Natl Acad Sci USA 101:13124–13131

    PubMed  CAS  Google Scholar 

  74. Ghitza UE, Fabbricatore AT, Prokopenko V, Pawlak AP, West MO (2003) Persistent cue-evoked activity of accumbens neurons after prolonged abstinence from self-administered cocaine. J Neurosci 23:7239–7245

    PubMed  CAS  Google Scholar 

  75. Goto Y, Grace AA (2005) Dopaminergic modulation of limbic and cortical drive of nucleus accumbens in goal-directed behavior. Nat Neurosci 8:805–812

    PubMed  CAS  Google Scholar 

  76. Gray JA, Kumari V, Lawrence N, Young AMJ (1999) Functions of the dopaminergic innervation of the nucleus accumbens. Psychobiology 27:225–235

    CAS  Google Scholar 

  77. Grill HJ, Norgren R (1978a) The taste reactivity test. I. Mimetic responses to gustatory stimuli in neurologically normal rats. Brain Res 143:263–279

    PubMed  CAS  Google Scholar 

  78. Grill HJ, Norgren R (1978b) The taste reactivity test. II. Mimetic responses to gustatory stimuli in chronic thalamic and chronic decerebrate rats. Brain Res 143:281–297

    PubMed  CAS  Google Scholar 

  79. Harris GC, Wimmer M, Aston-Jones G (2005) A role for lateral hypothalamic orexin neurons in reward seeking. Nature 437:556–559

    PubMed  CAS  Google Scholar 

  80. Hellemans KG, Dickinson A, Everitt BJ (2006) Motivational control of heroin seeking by conditioned stimuli associated with withdrawal and heroin taking by rats. Behav Neurosci 120:103–114

    PubMed  CAS  Google Scholar 

  81. Hernandez PJ, Andrzejewski ME, Sadeghian K, Panksepp JB, Kelley AE (2005) AMPA/kainate, NMDA, and dopamine D1 receptor function in the nucleus accumbens core: a context-limited role in the encoding and consolidation of instrumental memory. Learn Mem 12:285–295

    PubMed  Google Scholar 

  82. Hnasko TS, Sotak BN, Palmiter RD (2005) Morphine reward in dopamine-deficient mice. Nature 438:854–857

    PubMed  CAS  Google Scholar 

  83. Horvitz JC (2002) Dopamine gating of glutamatergic sensorimotor and incentive motivational input signals to the striatum. Behav Brain Res 137:65–74

    PubMed  CAS  Google Scholar 

  84. Hsu M, Bhatt M, Adolphs R, Tranel D, Camerer CF (2005) Neural systems responding to degrees of uncertainty in human decision-making. Science 310:1680–1683

    PubMed  CAS  Google Scholar 

  85. Hutcheson DM, Everitt BJ, Robbins TW, Dickinson A (2001) The role of withdrawal in heroin addiction: enhances reward or promotes avoidance? Nat Neurosci 4:943–947

    PubMed  CAS  Google Scholar 

  86. Hyman SE (2005) Addiction: a disease of learning and memory. Am J Psychiatry 162:1414–1422

    PubMed  Google Scholar 

  87. Hyman SE, Malenka RC (2001) Addiction and the brain: the neurobiology of compulsion and its persistence. Nat Rev Neurosci 2:695–703

    PubMed  CAS  Google Scholar 

  88. Ikemoto S, Panksepp J (1999) The role of nucleus accumbens dopamine in motivated behavior: a unifying interpretation with special reference to reward- seeking. Brain Res Rev 31:6–41

    PubMed  CAS  Google Scholar 

  89. Insel TR (2003) Is social attachment an addictive disorder? Physiol Behav 79:351–357

    PubMed  CAS  Google Scholar 

  90. Ito R, Dalley JW, Robbins TW, Everitt BJ (2002) Dopamine release in the dorsal striatum during cocaine-seeking behavior under the control of a drug-associated cue. J Neurosci 22:6247–6253

    PubMed  CAS  Google Scholar 

  91. Jarrett MM, Limebeer CL, Parker LA (2005) Effect of delta9-tetrahydrocannabinol on sucrose palatability as measured by the taste reactivity test. Physiol Behav 86:475–479

    PubMed  CAS  Google Scholar 

  92. Jenkins HM, Moore BR (1973) The form of the auto-shaped response with food or water reinforcers. J Exp Anal Behav 20:163–181

    PubMed  CAS  Google Scholar 

  93. Jones S, Bonci A (2005) Synaptic plasticity and drug addiction. Curr Opin Pharmacol 5:20–25

    PubMed  CAS  Google Scholar 

  94. Kaczmarek HJ, Kiefer SW (2000) Microinjections of dopaminergic agents in the nucleus accumbens affect ethanol consumption but not palatability. Pharmacol Biochem Behav 66:307–312

    PubMed  CAS  Google Scholar 

  95. Kalivas PW, Nakamura M (1999) Neural systems for behavioral activation and reward. Curr Opin Neurobiol 9:223–227

    PubMed  CAS  Google Scholar 

  96. Kalivas PW, Volkow ND (2005) The neural basis of addiction: a pathology of motivation and choice. Am J Psychiatry 162:1403–1413

    PubMed  Google Scholar 

  97. Kapur S (2003) Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia. Am J Psychiatry 160:13–23

    PubMed  Google Scholar 

  98. Kelley AE (2004a) Memory and addiction: shared neural circuitry and molecular mechanisms. Neuron 44:161–179

    PubMed  CAS  Google Scholar 

  99. Kelley AE (2004b) Ventral striatal control of appetitive motivation: role in ingestive behavior and reward-related learning. Neurosci Biobehav Rev 27:765–776

    PubMed  Google Scholar 

  100. Kelley AE, Baldo BA, Pratt WE (2005a) A proposed hypothalamic–thalamic–striatal axis for the integration of energy balance, arousal, and food reward. J Comp Neurol 493:72–85

    PubMed  CAS  Google Scholar 

  101. Kelley AE, Baldo BA, Pratt WE, Will MJ (2005b) Corticostriatal–hypothalamic circuitry and food motivation: integration of energy, action and reward. Physiol Behav 86:773–795

    PubMed  CAS  Google Scholar 

  102. Killcross AS, Dickinson A, Robbins TW (1994) Effects of the neuroleptic alpha-flupenthixol on latent inhibition in aversively- and appetitively-motivated paradigms: evidence for dopamine–reinforcer interactions. Psychopharmacology (Berl) 115:196–205

    CAS  Google Scholar 

  103. Knutson B, Fong GW, Adams CM, Varner JL, Hommer D (2001) Dissociation of reward anticipation and outcome with event-related fMRI. Neuroreport 12:3683–3687

    PubMed  CAS  Google Scholar 

  104. Koob GF, Le Moal M (2006) Neurobiology of addiction. Academic, London

    Google Scholar 

  105. Kringelbach ML (2005) The human orbitofrontal cortex: linking reward to hedonic experience. Nat Rev Neurosci 6:691–702

    PubMed  CAS  Google Scholar 

  106. Laviolette SR, Nader K, van der Kooy D (2002) Motivational state determines the functional role of the mesolimbic dopamine system in the mediation of opiate reward processes. Behav Brain Res 129:17–29

    PubMed  CAS  Google Scholar 

  107. LeDoux JE, Phelps EA (2000) Emotional networks in the brain. In: Lewis M, Haviland-Jones JM (eds) Handbook of emotions. Guilford, New York, pp 157–172

    Google Scholar 

  108. Levita L, Dalley JW, Robbins TW (2002) Nucleus accumbens dopamine and learned fear revisited: a review and some new findings. Behav Brain Res 137:115–127

    PubMed  CAS  Google Scholar 

  109. Leyton M, Boileau I, Benkelfat C, Diksic M, Baker G, Dagher A (2002) Amphetamine-induced increases in extracellular dopamine, drug wanting, and novelty seeking: a PET/[11C]raclopride study in healthy men. Neuropsychopharmacology 27:1027–1035

    PubMed  CAS  Google Scholar 

  110. Leyton M, Casey KF, Delaney JS, Kolivakis T, Benkelfat C (2005) Cocaine craving, euphoria, and self-administration: a preliminary study of the effect of catecholamine precursor depletion. Behav Neurosci 119:1619–1627

    PubMed  CAS  Google Scholar 

  111. Ljungberg T, Apicella P, Schultz W (1992) Responses of monkey dopamine neurons during learning of behavioral reactions. J Neurophysiol 67:145–163

    PubMed  CAS  Google Scholar 

  112. Loewenstein G, Schkade D (1999) Wouldn’t it be nice? Predicting future feelings. In: Kahneman D, Diener E, Schwarz N (eds) Well-being: the foundations of hedonic psychology. Russell Sage Foundation, New York, NY, pp 85–105

    Google Scholar 

  113. Mahler SV, Smith KS, Berridge KC (2004) What is the ‘motivational’ mechanism for the marijuana munchies? The effects of intra-accumbens anandamide on hedonic taste reactions to sucrose. Society for Neuroscience Conference, San Diego

    Google Scholar 

  114. Marinelli M, Rudick CN, Hu XT, White FJ (2006) Excitability of dopamine neurons: modulation and physiological consequences. CNS Neurol Disord Drug Targets 5:79–97

    PubMed  CAS  Google Scholar 

  115. McClure SM, Daw ND, Read Montague P (2003) A computational substrate for incentive salience. Trends Neurosci 26:423–428

    PubMed  CAS  Google Scholar 

  116. McClure SM, Laibson DI, Loewenstein G, Cohen JD (2004) Separate neural systems value immediate and delayed monetary rewards. Science 306:503–507

    PubMed  CAS  Google Scholar 

  117. McFarland K, Davidge SB, Lapish CC, Kalivas PW (2004) Limbic and motor circuitry underlying footshock-induced reinstatement of cocaine-seeking behavior. J Neurosci 24:1551–1560

    PubMed  CAS  Google Scholar 

  118. McGaugh JL (2002) Memory consolidation and the amygdala: a systems perspective. Trends Neurosci 25:456

    PubMed  CAS  Google Scholar 

  119. Miles FJ, Everitt BJ, Dickinson A (2003) Oral cocaine seeking by rats: action or habit? Behav Neurosci 117:927–938

    PubMed  Google Scholar 

  120. Miles FJ, Everitt BJ, Dalley JW, Dickinson A (2004) Conditioned activity and instrumental reinforcement following long-term oral consumption of cocaine by rats. Behav Neurosci 118:1331–1339

    PubMed  CAS  Google Scholar 

  121. Mirenowicz J, Schultz W (1996) Preferential activation of midbrain dopamine neurons by appetitive rather than aversive stimuli. Nature 379:449–451

    PubMed  CAS  Google Scholar 

  122. Montague PR, Hyman SE, Cohen JD (2004) Computational roles for dopamine in behavioural control. Nature 431:760–767

    PubMed  CAS  Google Scholar 

  123. Nader K, Bechara A, van der Kooy D (1997) Neurobiological constraints on behavioral models of motivation. Annu Rev Psychol 48:85–114

    PubMed  CAS  Google Scholar 

  124. Napier TC, Chrobak JJ (1992) Evaluations of ventral pallidal dopamine receptor activation in behaving rats. Neuroreport 3:609–611

    PubMed  CAS  Google Scholar 

  125. Narita M, Nagumo Y, Hashimoto S, Narita M, Khotib J, Miyatake M, Sakurai T, Yanagisawa M, Nakamachi T, Shioda S, Suzuki T (2006) Direct involvement of orexinergic systems in the activation of the mesolimbic dopamine pathway and related behaviors induced by morphine. J Neurosci 26:398–405

    PubMed  CAS  Google Scholar 

  126. Nelson A, Killcross S (2006) Amphetamine exposure enhances habit formation. J Neurosci 26:3805–3812

    PubMed  CAS  Google Scholar 

  127. Nesse RM (1990) Evolutionary explanations of emotions. Human Nat 1:261–289

    Google Scholar 

  128. Nicola SM, Taha SA, Kim SW, Fields HL (2005) Nucleus accumbens dopamine release is necessary and sufficient to promote the behavioral response to reward-predictive cues. Neuroscience 135:1025–1033

    PubMed  CAS  Google Scholar 

  129. Nocjar C, Panksepp J (2002) Chronic intermittent amphetamine pretreatment enhances future appetitive behavior for drug- and natural-reward: interaction with environmental variables. Behav Brain Res 128:189–203

    PubMed  CAS  Google Scholar 

  130. O’Brien CP, Gardner EL (2005) Critical assessment of how to study addiction and its treatment: human and non-human animal models. Pharmacol Ther 108:18–58

    PubMed  CAS  Google Scholar 

  131. O’Donnell P (2003) Dopamine gating of forebrain neural ensembles. Eur J Neurosci 17:429–435

    PubMed  Google Scholar 

  132. Onn SP, West AR, Grace AA (2000) Dopamine-mediated regulation of striatal neuronal and network interactions. Trends Neurosci 23:S48–S56

    PubMed  CAS  Google Scholar 

  133. Packard MG, White NM (1991) Dissociation of hippocampus and caudate nucleus memory systems by posttraining intracerebral injection of dopamine agonists. Behav Neurosci 105:295–306

    PubMed  CAS  Google Scholar 

  134. Panksepp J (1986) The neurochemistry of behavior. Annu Rev Psychol 37:77–107

    PubMed  CAS  Google Scholar 

  135. Panksepp J (2005) Affective consciousness: core emotional feelings in animals and humans. Conscious Cogn 14:30–80

    PubMed  Google Scholar 

  136. Parker L, Leeb K (1994) Amphetamine-induced modification of quinine palatability: analysis by the taste reactivity test. Pharmacol Biochem Behav 47:413–420

    PubMed  CAS  Google Scholar 

  137. Parker LA (1995) Chlordiazepoxide enhances the palatability of lithium-, amphetamine-, and saline-paired saccharin solution. Pharmacol Biochem Behav 50:345–349

    PubMed  CAS  Google Scholar 

  138. Parker LA, Maier S, Rennie M, Crebolder J (1992) Morphine- and naltrexone-induced modification of palatability: analysis by the taste reactivity test. Behav Neurosci 106:999–1010

    PubMed  CAS  Google Scholar 

  139. Pavlov IP (1927) Conditioned reflexes; an investigation of the physiological activity of the cerebral cortex. Oxford University Press, Humphrey Milford

    Google Scholar 

  140. Peciña S, Berridge KC (1995) Central enhancement of taste pleasure by intraventricular morphine. Neurobiology 3:269–280

    PubMed  Google Scholar 

  141. Peciña S, Berridge KC (2000) Opioid eating site in accumbens shell mediates food intake and hedonic ‘liking’: map based on microinjection Fos plumes. Brain Res 863:71–86

    PubMed  Google Scholar 

  142. Peciña S, Berridge KC (2005) Hedonic hot spot in nucleus accumbens shell: Where do mu-opioids cause increased hedonic impact of sweetness? J Neurosci 25:11777–11786

    PubMed  Google Scholar 

  143. Peciña S, Berridge KC, Parker LA (1997) Pimozide does not shift palatability: separation of anhedonia from sensorimotor suppression by taste reactivity. Pharmacol Biochem Behav 58:801–811

    PubMed  Google Scholar 

  144. Peciña S, Cagniard B, Berridge KC, Aldridge JW, Zhuang X (2003) Hyperdopaminergic mutant mice have higher “wanting” but not “liking” for sweet rewards. J Neurosci 23:9395–9402

    PubMed  Google Scholar 

  145. Peciña S, Schulkin J, Berridge KC (2006) Nucleus accumbens corticotropin-releasing factor increases cue-triggered motivation for sucrose reward: paradoxical positive incentive effects in stress? BMC Biol 4:8

    PubMed  Google Scholar 

  146. Peciña S, Smith KS, Berridge KC (2006) Hedonic hotspots in the brain. Neuroscientist 12(6):1–12

    Google Scholar 

  147. Petrovich GD, Holland PC, Gallagher M (2005) Amygdalar and prefrontal pathways to the lateral hypothalamus are activated by a learned cue that stimulates eating. J Neurosci 25:8295–8302

    PubMed  CAS  Google Scholar 

  148. Phillips GD, Robbins TW, Everitt BJ (1994) Mesoaccumbens dopamine–opiate interactions in the control over behaviour by a conditioned reinforcer. Psychopharmacology (Berl) 114:345–359

    CAS  Google Scholar 

  149. Phillips GD, Setzu E, Hitchcott PK (2003a) Facilitation of appetitive pavlovian conditioning by D-amphetamine in the shell, but not the core, of the nucleus accumbens. Behav Neurosci 117:675–684

    PubMed  CAS  Google Scholar 

  150. Phillips PE, Stuber GD, Heien ML, Wightman RM, Carelli RM (2003b) Subsecond dopamine release promotes cocaine seeking. Nature 422:614–618

    PubMed  CAS  Google Scholar 

  151. Piazza PV, Deminiere JM, Le Moal M, Simon H (1989) Factors that predict individual vulnerability to amphetamine self-administration. Science 245:1511–1513

    PubMed  CAS  Google Scholar 

  152. Redgrave P, Prescott TJ, Gurney K (1999) Is the short-latency dopamine response too short to signal reward error? Trends Neurosci 22:146–151

    PubMed  CAS  Google Scholar 

  153. Redish AD (2004) Addiction as a computational process gone awry. Science 306:1944–1947

    PubMed  CAS  Google Scholar 

  154. Reichmann H, Brecht MH, Koster J, Kraus PH, Lemke MR (2003) Pramipexole in routine clinical practice: a prospective observational trial in Parkinson’s disease. CNS Drugs 17:965–973

    PubMed  CAS  Google Scholar 

  155. Rescorla RA, Wagner AR (1972) A theory of Pavlovian conditioning: variations in the effectiveness of reinforcement and nonreinforcement. In: Black AH, Prokasy WF (eds) Classical conditioning II: current research and theory. Appleton-Century-Crofts, New York, pp 64–99

    Google Scholar 

  156. Reynolds SM, Berridge KC (2002) Positive and negative motivation in nucleus accumbens shell: bivalent rostrocaudal gradients for GABA-elicited eating, taste “liking”/“disliking” reactions, place preference/avoidance, and fear. J Neurosci 22:7308–7320

    PubMed  CAS  Google Scholar 

  157. Robbins TW, Everitt BJ (1982) Functional studies of the central catecholamines. Int Rev Neurobiol 23:303–365

    PubMed  CAS  Google Scholar 

  158. Robbins TW, Everitt BJ (1996) Neurobehavioural mechanisms of reward and motivation. Curr Opin Neurobiol 6:228–236

    PubMed  CAS  Google Scholar 

  159. Robbins TW, Everitt BJ (1999) Drug addiction: bad habits add up. Nature 398:567–570

    PubMed  CAS  Google Scholar 

  160. Robbins TW, Everitt BJ (2006) A role for mesencephalic dopamine in activation: commentary on Berridge (2006). Psychopharmacology (Berl), this issue

  161. Robertson EM, Cohen DA (2006) Understanding consolidation through the architecture of memories. Neuroscientist 12:261–271

    PubMed  Google Scholar 

  162. Robinson TE, Berridge KC (1993) The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res Rev 18:247–291

    PubMed  CAS  Google Scholar 

  163. Robinson TE, Berridge KC (2000) The psychology and neurobiology of addiction: an incentive-sensitization view. Addiction 95:91–117

    Google Scholar 

  164. Robinson TE, Berridge KC (2003) Addiction. Annu Rev Psychol 54:25–53

    PubMed  Google Scholar 

  165. Robinson S, Sandstrom SM, Denenberg VH, Palmiter RD (2005) Distinguishing whether dopamine regulates liking, wanting, and/or learning about rewards. Behav Neurosci 119:5–15

    PubMed  CAS  Google Scholar 

  166. Roitman MF, Stuber GD, Phillips PEM, Wightman RM, Carelli RM (2004) Dopamine operates as a subsecond modulator of food seeking. J Neurosci 24:1265–1271

    PubMed  CAS  Google Scholar 

  167. Roitman MF, Wheeler RA, Carelli RM (2005) Nucleus accumbens neurons are innately tuned for rewarding and aversive taste stimuli, encode their predictors, and are linked to motor output. Neuron 45:587–597

    PubMed  CAS  Google Scholar 

  168. Rolls ET (2005) Emotion explained. Oxford University Press, London

    Google Scholar 

  169. Rosse RB, Fay-McCarthy M, Collins JP Jr, Risher-Flowers D, Alim TN, Deutsch SI (1993) Transient compulsive foraging behavior associated with crack cocaine use. Am J Psychiatr 150:155–156

    PubMed  CAS  Google Scholar 

  170. Sahakian BJ, Robbins TW, Morgan MJ, Iversen SD (1975) The effects of psychomotor stimulants on stereotypy and locomotor activity in socially-deprived and control rats. Brain Res 84:195–205

    PubMed  CAS  Google Scholar 

  171. Salamone JD (1991) Behavioral pharmacology of dopamine systems: a new synthesis. In: Willner P, Scheel-Kruger J (eds) The mesolimbic dopamine system: from motivation to action. Wiley, New York, pp 599–611

    Google Scholar 

  172. Salamone JD (1994) The involvement of nucleus accumbens dopamine in appetitive and aversive motivation. Behav Brain Res 61:117–133

    PubMed  CAS  Google Scholar 

  173. Salamone JD, Correa M (2002) Motivational views of reinforcement: implications for understanding the behavioral functions of nucleus accumbens dopamine. Behav Brain Res 137:3–25

    PubMed  CAS  Google Scholar 

  174. Salamone JD, Cousins MS, Bucher S (1994) Anhedonia or anergia? Effects of haloperidol and nucleus accumbens dopamine depletion on instrumental response selection in a T-maze cost/benefit procedure. Behav Brain Res 65:221–229

    PubMed  CAS  Google Scholar 

  175. Salamone JD, Cousins MS, Snyder BJ (1997) Behavioral functions of nucleus accumbens dopamine: empirical and conceptual problems with the anhedonia hypothesis. Neurosci Biobehav Rev 21:341–359

    PubMed  CAS  Google Scholar 

  176. Salamone JD, Correa M, Mingote SM, Weber SM (2005) Beyond the reward hypothesis: alternative functions of nucleus accumbens dopamine. Curr Opin Pharmacol 5:34–41

    PubMed  CAS  Google Scholar 

  177. Sanders AE, Cagniard B, Manning SN, Zhuang X (2003) Dissecting aspects of motivation that are differentially modulated by dopamine and serotonin. Abstract Viewer/Itinerary Planner. Society for Neuroscience, Washington, DC

    Google Scholar 

  178. Sarter M, Nelson CL, Bruno JP (2005) Cortical cholinergic transmission and cortical information processing in schizophrenia. Schizophr Bull 31:117–138

    PubMed  Google Scholar 

  179. Schallert T, Whishaw IQ (1978) Two types of aphagia and two types of sensorimotor impairment after lateral hypothalamic lesions: observations in normal weight, dieted, and fattened rats. J Comp Physiol Psychol 92:720–741

    PubMed  CAS  Google Scholar 

  180. Schmajuk NA, Cox L, Gray JA (2001) Nucleus accumbens, entorhinal cortex and latent inhibition: a neural network model. Behav Brain Res 118:123–141

    PubMed  CAS  Google Scholar 

  181. Schoenbaum G, Setlow B (2005) Cocaine makes actions insensitive to outcomes but not extinction: implications for altered orbitofrontal–amygdalar function. Cereb Cortex 15:1162–1169

    PubMed  Google Scholar 

  182. Schultz W (1997) Dopamine neurons and their role in reward mechanisms. Curr Opin Neurobiol 7:191–197

    PubMed  CAS  Google Scholar 

  183. Schultz W (1998) Predictive reward signal of dopamine neurons. J Neurophysiol 80:1–27

    PubMed  CAS  Google Scholar 

  184. Schultz W (2002) Getting formal with dopamine and reward. Neuron 36:241–263

    PubMed  CAS  Google Scholar 

  185. Schultz W (2004) Neural coding of basic reward terms of animal learning theory, game theory, microeconomics and behavioural ecology. Curr Opin Neurobiol 14:139–147

    PubMed  CAS  Google Scholar 

  186. Schultz W (2006) Behavioral theories and the neurophysiology of reward. Annu Rev Psychol 57:87–115

    PubMed  Google Scholar 

  187. Schultz W, Dayan P, Montague PR (1997) A neural substrate of prediction and reward. Science 275:1593–1599

    PubMed  CAS  Google Scholar 

  188. Shaham Y, Shalev U, Lu L, de Wit H, Stewart J (2003) The reinstatement model of drug relapse: history, methodology and major findings. Psychopharmacology (Berl) 168:3–20

    CAS  Google Scholar 

  189. Sherrington CS (1906) The integrative action of the nervous system. C. Scribner’s, New York

    Google Scholar 

  190. Shippenberg TS, Heidbreder C (1995) Sensitization to the conditioned rewarding effects of cocaine: pharmacological and temporal characteristics. J Pharmacol Exp Ther 273:808–815

    PubMed  CAS  Google Scholar 

  191. Shizgal P (1999) On the neural computation of utility: implications from studies of brain stimulation reward. In: Kahneman D, Diener E, Schwarz N (eds) Well-being: the foundations of hedonic psychology. Russell Sage Foundation, New York, pp 500–524

    Google Scholar 

  192. Shizgal P, Fulton S, Woodside B (2001) Brain reward circuitry and the regulation of energy balance. Int J Obes 25:S17–S21

    CAS  Google Scholar 

  193. Sienkiewicz-Jarosz H, Scinska A, Kuran W, Ryglewicz D, Rogowski A, Wrobel E, Korkosz A, Kukwa A, Kostowski W, Bienkowski P (2005) Taste responses in patients with Parkinson’s disease. J Neurol Neurosurg Psychiatry 76:40–46

    PubMed  CAS  Google Scholar 

  194. Small DM, Jones-Gotman M, Dagher A (2003) Feeding-induced dopamine release in dorsal striatum correlates with meal pleasantness ratings in healthy human volunteers. Neuroimage 19:1709–1715

    PubMed  Google Scholar 

  195. Smith KS, Berridge KC (2005) The ventral pallidum and hedonic reward: neurochemical maps of sucrose “liking” and food intake. J Neurosci 25:8637–8649

    PubMed  CAS  Google Scholar 

  196. Smith-Roe SL, Kelley AE (2000) Coincident activation of NMDA and dopamine D-1 receptors within the nucleus accumbens core is required for appetitive instrumental learning. J Neurosci 20:7737–7742

    PubMed  CAS  Google Scholar 

  197. Söderpalm AHV, Berridge KC (2000) The hedonic impact and intake of food are increased by midazolam microinjection in the parabrachial nucleus. Brain Res 877:288–297

    PubMed  Google Scholar 

  198. Steiner JE (1973) The gustofacial response: observation on normal and anencephalic newborn infants. Symp Oral Sens Percept 4:254–278

    PubMed  Google Scholar 

  199. Steiner JE, Glaser D, Hawilo ME, Berridge KC (2001) Comparative expression of hedonic impact: affective reactions to taste by human infants and other primates. Neurosci Biobehav Rev 25:53–74

    PubMed  CAS  Google Scholar 

  200. Stellar JR, Brooks FH, Mills LE (1979) Approach and withdrawal analysis of the effects of hypothalamic stimulation and lesions in rats. J Comp Physiol Psychol 93:446–466

    PubMed  CAS  Google Scholar 

  201. Stricker EM, Zigmond MJ (1976) Brain catecholamines and the lateral hypothalamic syndrome. In: Novin D, Wyrwicka W, Bray G (eds) Hunger: basic mechanisms and clinical implications. Raven, New York, pp 19–32

    Google Scholar 

  202. Stricker EM, Zigmond MJ (1986) Brain monoamines, homeostasis, and adaptive behavior handbook of physiology: intrinsic regulatory systems of the brain. American Physiological Society, Bethesda, MD, pp 677–696

    Google Scholar 

  203. Taylor JR, Robbins TW (1984) Enhanced behavioural control by conditioned reinforcers following microinjections of d-amphetamine into the nucleus accumbens. Psychopharmacology (Berl) 84:405–412

    CAS  Google Scholar 

  204. Taylor JR, Robbins TW (1986) 6-Hydroxydopamine lesions of the nucleus accumbens, but not of the caudate nucleus, attenuate enhanced responding with reward-related stimuli produced by intra-accumbens d-amphetamine. Psychopharmacology (Berl) 90:390–397

    CAS  Google Scholar 

  205. Thorndike EL (1898) Animal intelligence: an experimental study of the associative processes in animals. Macmillan, New York

    Google Scholar 

  206. Thorndike EL (1911) Animal intelligence: experimental studies. Macmillan, New York

    Google Scholar 

  207. Thut G, Schultz W, Roelcke U, Nienhusmeier M, Missimer J, Maguire RP, Leenders KL (1997) Activation of the human brain by monetary reward. Neuroreport 8:1225–1228

    PubMed  CAS  Google Scholar 

  208. Tindell AJ, Berridge KC, Aldridge JW (2004) Ventral pallidal representation of pavlovian cues and reward: population and rate codes. J Neurosci 24:1058–1069

    PubMed  CAS  Google Scholar 

  209. Tindell AJ, Berridge KC, Zhang J, Peciña S, Aldridge JW (2005) Ventral pallidal neurons code incentive motivation: amplification by mesolimbic sensitization and amphetamine. Eur J Neurosci 22:2617–2634

    PubMed  Article  Google Scholar 

  210. Tindell AJ, Smith KS, Pecina S, Berridge KC, Aldridge JW (2006) Ventral pallidum firing codes hedonic reward: when a bad taste turns good. J Neurophysiol 96:2399–2409

    Google Scholar 

  211. Toates F (1986) Motivational systems. Cambridge University Press

  212. Tobler PN, Dickinson A, Schultz W (2003) Coding of predicted reward omission by dopamine neurons in a conditioned inhibition paradigm. J Neurosci 23:10402–10410

    PubMed  CAS  Google Scholar 

  213. Tobler PN, Fiorillo CD, Schultz W (2005a) Adaptive coding of reward value by dopamine neurons. Science 307:1642–1645

    PubMed  CAS  Google Scholar 

  214. Tobler PN, O’Doherty JP, Dolan RJ, Schultz W (2005b) Human neural learning depends on reward prediction errors in the blocking paradigm. J Neurophysiol (1):301–310

    Google Scholar 

  215. Tomie A (1996) Locating reward cue at response manipulandum (CAM) induces symptoms of drug abuse. Neurosci Biobehav Rev 20:31

    Google Scholar 

  216. Ungless MA, Magill PJ, Bolam JP (2004) Uniform inhibition of dopamine neurons in the ventral tegmental area by aversive stimuli. Science 303:2040–2042

    PubMed  CAS  Google Scholar 

  217. Uslaner JM, Acerbo MJ, Jones SA, Robinson TE (2006) The attribution of incentive salience to a stimulus that signals an intravenous injection of cocaine. Behav Brain Res 169(2):320–324

    PubMed  CAS  Google Scholar 

  218. Vanderschuren LJ, Everitt BJ (2005) Behavioral and neural mechanisms of compulsive drug seeking. Eur J Pharmacol 526:77–88

    PubMed  CAS  Google Scholar 

  219. Vanderschuren LJMJ, Everitt BJ (2004) Drug seeking becomes compulsive after prolonged cocaine self-administration. Science 305:1017–1019

    PubMed  CAS  Google Scholar 

  220. Vanderschuren LJMJ, Kalivas PW (2000) Alterations in dopaminergic and glutamatergic transmission in the induction and expression of behavioral sensitization: a critical review of preclinical studies. Psychopharmacology (Berl) 151:99–120

    CAS  Google Scholar 

  221. Vanderschuren LJMJ, Di Ciano P, Everitt BJ (2005) Involvement of the dorsal striatum in cue-controlled cocaine seeking. J Neurosci 25:8665–8670

    PubMed  CAS  Google Scholar 

  222. Vezina P (2004) Sensitization of midbrain dopamine neuron reactivity and the self-administration of psychomotor stimulant drugs. Neurosci Biobehav Rev 27:827–839

    PubMed  CAS  Google Scholar 

  223. Vezina P, Lorrain DS, Arnold GM, Austin JD, Suto N (2002) Sensitization of midbrain dopamine neuron reactivity promotes the pursuit of amphetamine. J Neurosci 22:4654–4662

    PubMed  CAS  Google Scholar 

  224. Volkow ND, Wise RA (2005) How can drug addiction help us understand obesity? Nat Neurosci 8:555–560

    PubMed  CAS  Google Scholar 

  225. Volkow ND, Wang GJ, Fowler JS, Logan J, Gatley SJ, Wong C, Hitzemann R, Pappas NR (1999) Reinforcing effects of psychostimulants in humans are associated with increases in brain dopamine and occupancy of D-2 receptors. J Pharmacol Exp Ther 291:409–415

    PubMed  CAS  Google Scholar 

  226. Volkow ND, Fowler JS, Wang GJ, Ding YS, Gatley SJ (2002a) Role of dopamine in the therapeutic and reinforcing effects of methylphenidate in humans: results from imaging studies. Eur Neuropsychopharmacol 12:557–566

    PubMed  CAS  Google Scholar 

  227. Volkow ND, Wang GJ, Fowler JS, Logan J, Jayne M, Franceschi D, Wong C, Gatley SJ, Gifford AN, Ding YS, Pappas N (2002b) “Nonhedonic” food motivation in humans involves dopamine in the dorsal striatum and methylphenidate amplifies this effect. Synapse 44:175–180

    PubMed  CAS  Google Scholar 

  228. Volkow ND, Wang G-J, Telang F, Fowler JS, Logan J, Childress A-R, Jayne M, Ma Y, Wong C (2006) Cocaine cues and dopamine in dorsal striatum: mechanism of craving in cocaine addiction. J Neurosci 26:6583–6588

    PubMed  CAS  Google Scholar 

  229. Waelti P, Mirenowicz J, Dickinson A, Schultz W (1998) Activity of primate dopamine neurons in a discrimination and blocking paradigm. Eur J Neurosci 10:302

    Google Scholar 

  230. Waelti P, Dickinson A, Schultz W (2001) Dopamine responses comply with basic assumptions of formal learning theory. Nature 412:43–48

    PubMed  CAS  Google Scholar 

  231. Wakabayashi KT, Fields HL, Nicola SM (2004) Dissociation of the role of nucleus accumbens dopamine in responding to reward-predictive cues and waiting for reward. Behav Brain Res 154:19–30

    PubMed  CAS  Article  Google Scholar 

  232. Wang GJ, Volkow ND, Logan J, Pappas NR, Wong CT, Zhu W, Netusil N, Fowler JS (2001) Brain dopamine and obesity. Lancet 357:354–357

    PubMed  CAS  Google Scholar 

  233. Wang GJ, Volkow ND, Chang L, Miller E, Sedler M, Hitzemann R, Zhu W, Logan J, Ma Y, Fowler JS (2004) Partial recovery of brain metabolism in methamphetamine abusers after protracted abstinence. Am J Psychiatry 161:242–248

    PubMed  Google Scholar 

  234. Washton AM, Stone-Washton N (1993) Outpatient treatment of cocaine and crack addiction: a clinical perspective. NIDA Res Monogr 135:15–30

    PubMed  CAS  Google Scholar 

  235. Watson JB (1913) Psychology as the behaviourist views it. Psychol Rev 20:158–177

    Google Scholar 

  236. Weingarten HP, Martin GM (1989) Mechanisms of conditioned meal initiation. Physiol Behav 45:735–740

    PubMed  CAS  Google Scholar 

  237. Wickelgren I (1997) Neuroscience: getting the brain’s attention. Science 278:35–37

    PubMed  CAS  Google Scholar 

  238. Wickens J, Reynolds J, Hyland B (2003) Neural mechanisms of reward-related motor learning. Curr Opin Neurobiol 13:685–690

    PubMed  CAS  Google Scholar 

  239. Wilson C, Nomikos GG, Collu M, Fibiger HC (1995) Dopaminergic correlates of motivated behavior: importance of drive. J Neurosci 15:5169–5178

    PubMed  CAS  Google Scholar 

  240. Winkielman P, Berridge KC, Wilbarger JL (2005) Unconscious affective reactions to masked happy versus angry faces influence consumption behavior and judgments of value. Pers Soc Psychol Bull 31:121–135

    PubMed  Google Scholar 

  241. Wise RA (1980) The dopamine synapse and the notion of ‘pleasure centers’ in the brain. Trends Neurosci 3:91–95

    CAS  Google Scholar 

  242. Wise RA (1982) Neuroleptics and operant behavior: the anhedonia hypothesis. Behav Brain Sci 5:39–87

    Article  Google Scholar 

  243. Wise RA (1985) The anhedonia hypothesis: Mark III. Behav Brain Sci 8:178–186

    Google Scholar 

  244. Wise RA (2004a) Dopamine, learning and motivation. Nat Rev Neurosci 5:483–494

    PubMed  CAS  Google Scholar 

  245. Wise RA (2004b) Drive, incentive, and reinforcement: the antecedents and consequences of motivation. Nebr Symp Motiv 50:159–195

    PubMed  Google Scholar 

  246. Wise RA (2006) Role of brain dopamine in food reward and reinforcement. Philos Trans R Soc Lond B Biol Sci 361:1149–1158

    PubMed  CAS  Google Scholar 

  247. Wolterink G, Phillips G, Cador M, Donselaar-Wolterink I, Robbins TW, Everitt BJ (1993) Relative roles of ventral striatal D1 and D2 dopamine receptors in responding with conditioned reinforcement. Psychopharmacology (Berl) 110:355–364

    CAS  Google Scholar 

  248. Wyvell CL, Berridge KC (2000) Intra-accumbens amphetamine increases the conditioned incentive salience of sucrose reward: enhancement of reward “wanting” without enhanced “liking” or response reinforcement. J Neurosci 20:8122–8130

    PubMed  CAS  Google Scholar 

  249. Wyvell CL, Berridge KC (2001) Incentive-sensitization by previous amphetamine exposure: increased cue-triggered ‘wanting’ for sucrose reward. J Neurosci 21:7831–7840

    PubMed  CAS  Google Scholar 

  250. Yin HH, Zhuang X, Balleine BW (2006) Instrumental learning in hyperdopaminergic mice. Neurobiol Learn Mem (3):238–283

    Google Scholar 

  251. Zahm DS (2000) An integrative neuroanatomical perspective on some subcortical substrates of adaptive responding with emphasis on the nucleus accumbens. Neurosci Biobehav Rev 24:85–105

    PubMed  CAS  Google Scholar 

  252. Zahm DS (2006) The evolving theory of basal forebrain functional–anatomical ‘macrosystems’. Neurosci Biobehav Rev 30(2):148–172

    PubMed  Google Scholar 

  253. Zhang J, Tindell A, Berridge K, Aldridge J (2005) Profile analysis of integrative coding in ventral pallidal neurons. Society for Neuroscience, Washington, DC

    Google Scholar 

  254. Zheng HY, Corkern M, Stoyanova I, Patterson LM, Tian R, Berthoud HR (2003) Peptides that regulate food intake—appetite-inducing accumbens manipulation activates hypothalamic orexin neurons and inhibits POMC neurons. Am J Physiol Regul Integr Comp Physiol 284:R1436–R1444

    PubMed  CAS  Google Scholar 

  255. Zhou QY, Palmiter RD (1995) Dopamine-deficient mice are severely hypoactive, adipsic, and aphagic. Cell 83:1197–1209

    PubMed  CAS  Google Scholar 

  256. Zhuang X, Oosting RS, Jones SR, Gainetdinov PR, Miller GW, Caron MG, Hen R (2001) Hyperactivity and impaired response habituation in hyperdopaminergic mice. Proc Natl Acad Sci USA 98:1982–1987

    PubMed  CAS  Google Scholar 

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Acknowledgements

I am grateful to many colleagues who have participated in developing these ideas especially my long-term Michigan collaborators Terry Robinson, who co-developed the incentive salience hypothesis at every step and developed the incentive-sensitization theory, and J. Wayne Aldridge, who has led investigations into its neural coding. I am grateful also to Jill Becker, who arranged the Gordon Conference 2005 debate, and to the editors of this special issue, who arranged for it to be put to paper. Talented colleagues conducted the experiments in our labs that produced the data mentioned here, especially Susana Peciña, Cindy Wyvell, Amy Tindell, Jun Zhang, Casey Cromwell, Sheila Reynolds, Kyle Smith, Stephen Mahler, and Alexis Faure. Xiaoxi Zhuang and Barbara Cagniard also collaborated at a distance on the hyperdopaminergic mice project. Our experiments were supported by NIH (DA015188, DA017752, and MH63649).

This essay was written while on leave at the University of Cambridge, supported as a J.S. Guggenheim Fellow. I am deeply indebted to the kind generosity of Barry Everitt, Anthony Dickinson, Trevor Robbins, Wolfram Schultz, Jeff Dalley, Nicky Clayton, Paul Fletcher, Barbara Sahakian, Angela Roberts, Andrew Calder, Andrew Lawrence, Graham Murray, Todd Braver, Deanna Barch, Anthony Marcel, Susan Jones, Phil Corlett, and many other Cambridge colleagues and students in the Department of Experimental Psychology, Downing College, the Behavioral and Clinical Neuroscience Institute, and the MRC Cognition and Brain Sciences Unit for stimulating discussions and hospitality during the academic year in Cambridge.

Finally, I especially thank Barry Everitt, Terry Robinson, Wolfram Schultz, Trevor Robbins, J. Wayne Aldridge, Jill Becker, Martin Sarter, Anthony Dickinson, Joshua Berke, Jeff Dalley, Jaak Panksepp, John Salamone, Susana Pecina, Kyle Smith, Steve Mahler and anonymous reviewers for enormously helpful comments on an earlier draft of this essay.

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Movie 1

Hedonic taste reactions. Examples of positive facial ‘liking’ reactions elicited by sweet taste of sucrose solution from newborn human infants (via oral dropper) and adult rats (via oral cannula). Negative ‘disliking’ reactions elicited by bitter taste of quinine solution. Human infant reactions from Steiner et al. (2001); Rat reactions from Berridge (2000) (MPG 12 mb)

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Berridge, K.C. The debate over dopamine’s role in reward: the case for incentive salience. Psychopharmacology 191, 391–431 (2007). https://doi.org/10.1007/s00213-006-0578-x

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Keywords

  • Accumbens
  • Reward
  • Opioid
  • Dopamine
  • Basal forebrain
  • Aversion
  • Associative learning
  • Appetite
  • Addiction