Review Article | Published:

Dopamine, learning and motivation

Nature Reviews Neuroscience volume 5, pages 483494 (2004) | Download Citation

Subjects

Abstract

The hypothesis that dopamine is important for reward has been proposed in a number of forms, each of which has been challenged. Normally, rewarding stimuli such as food, water, lateral hypothalamic brain stimulation and several drugs of abuse become ineffective as rewards in animals given performance-sparing doses of dopamine antagonists. Dopamine release in the nucleus accumbens has been linked to the efficacy of these unconditioned rewards, but dopamine release in a broader range of structures is implicated in the 'stamping-in' of memory that attaches motivational importance to otherwise neutral environmental stimuli.

Key points

  • Brain dopamine has been linked to both motor and motivational functions. Several motivational hypotheses have been challenged and found inadequate, but it remains clear that dopamine is vital for the 'stamping-in' of stimulus–reward and response–reward associations.

  • Stimulus–reward associations are, in turn, crucial for the subsequent motivation in a previous-reward situation. Response habits are triggered by environmental stimuli that have been previously associated with reward, and the initiation of such response habits is not dependent on immediate dopamine function. If repeated with dopamine function blocked, however, the old stimulus–reward associations are extinguished and response motivation progressively weakens.

  • While the motivational effectiveness of reward-associated stimuli does not require immediate dopamine function, phasic dopamine elevations can nonetheless amplify stimulus effectiveness. This amplification is thought to be a dopamine function in the nucleus accumbens.

  • The role of dopamine in the stamping-in of reward associations might be much less localized. Dopamine seems to have important roles in the consolidation of memory in various structures — structures that are linked to different kinds of learning or to the learning of different things.

  • A full appreciation of the role of dopamine in motivation must be on the basis of an understanding of not only the role of dopamine in immediate behavioural arousal, but also its role in the learning and memory of learned motivational stimuli.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    Drugs affecting movement disorders. Ann. Rev. Pharmacol. 14, 91–113 (1974).

  2. 2.

    & Increased lever pressing for amphetamine after pimozide in rats: implications for a dopamine theory of reward. Science 187, 547–549 (1975).

  3. 3.

    & Pimozide-induced extinction of intracranial self-stimulation: response patterns rule out motor or performance deficits. Brain Res. 103, 377–380 (1976).

  4. 4.

    , & Neuroleptic-induced attenuation of brain stimulation reward in rats. J. Comp. Physiol. Psychol. 92, 661–671 (1978).

  5. 5.

    , , & Neuroleptic-induced 'anhedonia' in rats: pimozide blocks reward quality of food. Science 201, 262–264 (1978).

  6. 6.

    , & Pimozide attenuates lever pressing for water reinforcement in rats. Pharmacol. Biochem. Behav. 14, 201–205 (1981).

  7. 7.

    & Haloperidol induces a partial reinforcement extinction effect in rats: implications for a dopamine involvement in food reward. Pharmacol. Biochem. Behav. 25, 813–821 (1986).

  8. 8.

    & A partial reinforcement extinction effect in water-reinforced rats intermittently treated with haloperidol. Pharmacol. Biochem. Behav. 25, 1231–1235 (1986).

  9. 9.

    & Haloperidol differentially affects reinforcement and motivational processes in rats running an alley for intravenous heroin. Psychopharmacology 122, 346–350 (1995). A particularly clear demonstration of how neuroleptics impair reinforcement before they impair motivation.

  10. 10.

    & Haloperidol does not affect motivational processes in an operant runway model of food-seeking behavior. Behav. Neurosci. 112, 630–635 (1998).

  11. 11.

    Catecholamines and self-stimulation: reward and performance effects dissociated. Pharmacol. Biochem. Behav. 9, 813–820 (1978).

  12. 12.

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

  13. 13.

    & Haloperidol does not attenuate conditioned place preferences or locomotor activation produced by food- or heroin-predictive discriminative cues. Pharmacol. Biochem. Behav. 62, 631–641 (1999).

  14. 14.

    & Effects of naloxone and pimozide on initiation and maintenance measures of free feeding. Brain Res. 368, 62–68 (1986). A particularly clear demonstration that neuroleptics attenuate the ability of food to maintain eating long before they attenuate the animal's motivation to feed.

  15. 15.

    , & From motivation to action: functional interface between the limbic system and the motor system. Progr. Neurobiol. 14, 69–97 (1980). This classic paper, more than any other, identified nucleus accumbens dopamine with motivational function.

  16. 16.

    & Brain dopamine and reward. Ann. Rev. Psychol. 40, 191–225 (1989).

  17. 17.

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

  18. 18.

    Adipsia and aphagia after 6-hydroxydopamine induced degeneration of the nigro-striatal dopamine system. Acta Physiol. Scand. (Suppl.) 367, 95–122 (1971).

  19. 19.

    , & Effect of lateral hypothalamic injections of 6-hydroxydopamine on food and water intake in rats. Nature New Biol. 235, 27–29 (1972).

  20. 20.

    , , & Different behavioral responses to L-DOPA after anterolateral or posterolateral hypothalamic injections of 6-hydroxydopamine. Brain Res. 132, 507–520 (1977).

  21. 21.

    The arousal function of central catecholamine neurons. Ann. NY Acad. Sci. 270, 45–56 (1976).

  22. 22.

    in Nebraska Symposium on Motivation (ed. Jones, M. R.) 1–42 (Univ. Nebraska Press, Lincoln, 1959).

  23. 23.

    & Comparative involvement of dopamine and noradrenaline in rate-free self-stimulation in substantia nigra, lateral hypothalamus, and mesencephalic central gray. Naunyn-Schmiedeberg's Arch. Pharmacol. 284, 167–194 (1974).

  24. 24.

    & Pimozide-induced extinction in rats: stimulus control of responding rules out motor deficit. Pharmacol. Biochem. Behav. 11, 71–75 (1979). A nice demonstration of sensory control of responding under neuroleptic treatment. This study refutes the notion that neuroleptic-induced response deficits are the result of motor impairment or vulnerability to fatigue.

  25. 25.

    , , & Does pimozide block the reinforcing effect of brain stimulation? Pharmacol. Biochem. Behav. 17, 769–781 (1982).

  26. 26.

    & Blockade of cocaine reinforcement in rats with the dopamine receptor blocker pimozide, but not with the noradrenergic blockers phentolamine or phenoxybenzamine. Can. J. Psychol. 31, 195–203 (1977).

  27. 27.

    & Pimozide attenuates acquisition of lever pressing for food in rats. Pharmacol. Biochem. Behav. 15, 655–656 (1981).

  28. 28.

    , & Dissociation of Pavlovian and instrumental incentive learning under dopamine antagonists. Behav. Neurosci. 114, 468–483 (2000).

  29. 29.

    , , & Neurochemical mediation of reward: a significant role for dopamine. Pharmacol. Biochem. Behav. 1, 23–28 (1973).

  30. 30.

    , & On the role of ascending catecholaminergic systems in intravenous self-administration of cocaine. Pharmacol. Biochem. Behav. 6, 615–620 (1977).

  31. 31.

    , & Self-stimulation at the lateral hypothalamus and locus coeruleus after specific unilateral lesions of the dopamine system. Brain Res. 146, 123–140 (1978).

  32. 32.

    , , & Extinction and recovery of cocaine self-administration following 6-OHDA lesions of the nucleus accumbens. Pharmacol. Biochem. Behav. 12, 781–787 (1980).

  33. 33.

    & Disruption of cocaine self-administration following 6-hydroxydopamine lesions of the ventral tegmental area in rats. Pharmacol. Biochem. Behav. 17, 901–904 (1982).

  34. 34.

    Drugs and reinforcement mechanisms: a critical review of the catecholamine theory. Ann. Rev. Pharmacol. Toxicol. 18, 37–56 (1978).

  35. 35.

    Catecholamine theories of reward: a critical review. Brain Res. 152, 215–247 (1978).

  36. 36.

    in The Neuropharmacological Basis of Reward (eds Liebman, J. M. & Cooper, S. J.) 377–424 (Oxford Univ. Press, Oxford, 1989).

  37. 37.

    , & Major attenuation of food reward with performance-sparing doses of pimozide in the rat. Can. J. Psychol. 32, 77–85 (1978).

  38. 38.

    in Progress in Psychobiology and Physiological Psychology (eds Morrison, A. & Fluharty, S.) 83–144 (Academic, New York, 1995).

  39. 39.

    , , & Pimozide-induced suppression of responding: evidence against a block of food reward. Pharmacol. Biochem. Behav. 12, 917–923 (1980).

  40. 40.

    The dopamine anhedonia hypothesis: a pharmacological phrenology. Behav. Brain Sci. 5, 63–64 (1982).

  41. 41.

    , & Response artifact in the measurement of neuroleptic-induced anhedonia. Science 213, 357–359 (1981).

  42. 42.

    , & Behavioral functions of nucleus accumbens dopamine: empirical and conceptual problems with the anhedonia hypothesis. Neurosci. Biobehav. Rev. 21, 341–359 (1997).

  43. 43.

    The role of dopamine in locomotor activity and learning. Brain Res. Rev. 6, 173–196.

  44. 44.

    , & Attenuation by haloperidol of place preference conditioning using food reinforcement. Psychopharmacology 77, 379–382 (1982).

  45. 45.

    & Heroin reward is dependent on a dopaminergic substrate. Life Sci. 29, 1881–1886 (1981).

  46. 46.

    , & Dopaminergic substrates of amphetamine-induced place preference conditioning. Brain Res. 253, 185–193 (1982).

  47. 47.

    , & Attenuation of heroin reward in rats by disruption of the mesolimbic dopamine system. Psychopharmacology 79, 278–283 (1983).

  48. 48.

    , & Intravenous cocaine-induced place preference: attenuation by haloperidol. Behav. Brain. Res. 26, 57–62 (1987).

  49. 49.

    & Rewarding actions of phencyclidine and related drugs in nucleus accumbens shell and frontal cortex. J. Neurosci. 16, 3112–3122 (1996).

  50. 50.

    Sensory and cognitive functions of the basal ganglia. Curr. Opin. Neurobiol. 7, 157–163 (1997).

  51. 51.

    The MPTP-treated primate as a model of motor complications in PD: primate model of motor complications. Neurology 61, (Suppl. 3) S4–11 (2003).

  52. 52.

    Neuropsychological interpretation of the effects of drive and incentive-motivation on general activity and instrumental behavior. Psychol. Rev. 75, 1–22 (1968).

  53. 53.

    Self-stimulation aftereffects and runway performance in the rat. J. Comp. Physiol. Psychol. 56, 673–678 (1963).

  54. 54.

    , & Parametric analysis of brain stimulation reward in the rat: I. The transient process and the memory-containing process. J. Comp. Physiol. Psychol. 87, 848–859 (1974). This classic paper distinguishes clearly between the priming and reinforcing functions of brain stimulation reward. The first decays in seconds, whereas the second is effective for weeks.

  55. 55.

    & Self-administration of D-amphetamine by rats. Psychopharmacologia 12, 158–163 (1968).

  56. 56.

    , & Specific modulation of brain stimulation reward by haloperidol. Pharmacol. Biochem. Behav. 10, 937–940 (1979). Although it is couched in terms of reinforcement, this study measures the priming effects of free brain stimulation on the latency to lever-press for more.

  57. 57.

    , & Pimozide blocks reinforcement but not priming from MFB stimulation in the rat. Pharmacol. Biochem. Behav. 17, 783–787 (1982). This study shows that the priming effect of stimulation undergoes an extinction-like decline under neuroleptic treatment, indicating that even the rapidly decaying priming effect is partially conditioned.

  58. 58.

    , , & Reinstatement and spontaneous recovery of nicotine seeking in rats. Psychopharmacology 130, 396–403 (1997).

  59. 59.

    & Reinstatement of cocaine-reinforced responding in the rat. Psychopharmacology 75, 134–143 (1981).

  60. 60.

    , & Bromocriptine self-administration and bromocriptine-reinstatement of cocaine-trained and heroin-trained lever-pressing in rats. Psychopharmacology 100, 355–360 (1990).

  61. 61.

    , , , & Subsecond dopamine release promotes cocaine seeking. Nature 422, 614–618 (2003).

  62. 62.

    & Glutamate transmission in the nucleus accumbens mediates relapse in cocaine addiction. J. Neurosci. 20, RC89 (2000).

  63. 63.

    , , , & Dopamine operates as a subsecond modulator of food seeking. J. Neurosci. 24, 1265–1271 (2004).

  64. 64.

    & 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 (2000).

  65. 65.

    Quantitative variation of incentive and performance in the white rat. Am. J. Psychol. 55, 467–517 (1942).

  66. 66.

    , & Role of unconditioned and conditioned drug effects in the self-administration of opiates and stimulants. Psychol. Rev. 91, 251–268 (1984).

  67. 67.

    The role of hunger in the T-maze learning for food by rats. J. Comp. Physiol. Psychol. 62, 341–349 (1966).

  68. 68.

    Resistance to satiation. Anim. Behav. 22, 449–466 (1974). References 67 and 68 show that response initiation depends more on the animal's habit strength based on recent reinforcement history than on the current hunger level of the animal. The parallel between the role of hunger and the role of dopamine in response initiation in well-trained animals is central to the suggestions of the current review.

  69. 69.

    & Pimozide attenuates free feeding: best scores analysis reveals a motivational deficit. Psychopharmacology 84, 446–451 (1984).

  70. 70.

    , & Effects of SCH 23390 on latency and speed measures of deprivation-induced feeding. Psychobiology 16, 207–212 (1988).

  71. 71.

    , & Responses of monkey dopamine neurons during learning of behavioral reactions. J. Neurophysiol. 67, 145–163 (1992).

  72. 72.

    , & Responses of monkey dopamine neurons to reward and conditioned stimuli during successive steps of learning a delayed response task. J. Neurosci. 13, 900–913 (1993).

  73. 73.

    & Food reward and cocaine increase extracellular dopamine in the nucleus accumbens as measured by microdialysis. Life Sci. 42, 1705–1712 (1988).

  74. 74.

    , , & Elevations of nucleus accumbens dopamine and DOPAC levels during intravenous heroin self-administration. Synapse 21, 140–148 (1995).

  75. 75.

    et al. Fluctuations in nucleus accumbens dopamine concentration during intravenous cocaine self-administration in rats. Psychopharmacology 120, 10–20 (1995).

  76. 76.

    , , & Dopamine fluctuations in the nucleus accumbens during maintenance, extinction, and reinstatement of intravenous D-amphetamine self-administration. J. Neurosci. 19, 4102–4109 (1999).

  77. 77.

    & Enhanced behavioural control by conditioned reinforcers produced by intracerebral injections of D-amphetamine in the rat. Psychopharmacology 84, 405–412 (1984).

  78. 78.

    & 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 90, 390–397 (1986).

  79. 79.

    et al. SPECT imaging of striatal dopamine release after amphetamine challenge. J. Nuc. Med. 36, 1182–1190 (1995).

  80. 80.

    et al. 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 (1999).

  81. 81.

    et al. Amphetamine-induced dopamine release in human ventral striatum correlates with euphoria. Biol. Psychiatry 49, 81–96 (2001).

  82. 82.

    , & Blockade of intravenous amphetamine euphoria in man. Clin. Pharmacol. Ther. 12, 889–896 (1971).

  83. 83.

    , & Clinical trials with amphetamine-blocking drugs. Psychiatr. Neurol. Neurochir. 75, 225–226 (1972).

  84. 84.

    & High dose pimozide does not block amphetamine-induced euphoria in normal volunteers. Pharmacol. Biochem. Behav. 56, 265–272 (1997).

  85. 85.

    et al. Cocaine dependence and D2 receptor availability in functional subdivisions of the striatum: relationship with cocaine-seeking behavior. Neuropsychopharmacology (in the press).

  86. 86.

    & Schedules using noxious stimuli. 3. Responding maintained with response produced electric shocks. J. Exper. Anal. Behav. 11, 819–838 (1968).

  87. 87.

    & Self-poisoning and self-injury in adults. Clin. Med. 2, 509–512 (2002).

  88. 88.

    & Smoked and intravenous cocaine in humans: acute tolerance, cardiovascular and subjective effects. J. Pharmacol. Exp. Ther. 257, 247–261 (1991).

  89. 89.

    et al. The reinforcing and subjective effects of morphine in post-addicts: a dose-response study. J. Pharmacol. Exp. Ther. 259, 1165–1173 (1991).

  90. 90.

    Subjective and behavioural effects of nicotine in humans: some sources of individual variation. Prog. Brain Res. 79, 289–302 (1989).

  91. 91.

    in Contemporary Research in Behavioral Pharmacology (eds Blackman, D. E. & Sanger, D. J.) 325–390 (Plenum, New York, 1978).

  92. 92.

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

  93. 93.

    , & Taste reactivity analysis of 6-hydroxydopamine-induced aphagia: implications for arousal and anhedonia hypotheses of dopamine function. Behav. Neurosci. 103, 36–45 (1989).

  94. 94.

    , & Pimozide does not shift palatability: separation of anhedonia from sensorimotor suppression by taste reactivity. Pharmacol. Biochem. Behav. 58, 801–811 (1997).

  95. 95.

    , & Effects of pimozide on the hedonic properties of sucrose: analysis by the taste reactivity test. Pharmacol. Biochem. Behav. 39, 895–901 (1991).

  96. 96.

    & The taste reactivity test. II. Mimetic responses to gustatory stimuli in chronic thalamic and chronic decerebrate rats. Brain Res. 143, 281–297 (1978).

  97. 97.

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

  98. 98.

    , , & Sodium depletion enhances salt palatability in rats. Behav. Neurosci. 98, 652–660 (1984).

  99. 99.

    & The mind of an addicted brain: neural sensitization of wanting and liking. Curr. Direct. Psychol. Sci. 4, 71–76 (1995).

  100. 100.

    Sensorimotor modulation and the variable action pattern (VAP): toward a noncircular definition of drive and motivation. Psychobiology 15, 7–20 (1987).

  101. 101.

    , , & Heroin and cocaine intravenous self-administration in rats: mediation by separate neural systems. Psychopharmacology 78, 204–209 (1982).

  102. 102.

    , & 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 (1994).

  103. 103.

    & in The Neurobiology of the Nucleus Accumbens (eds Chronister, R. B. & DeFrance, J. F.) 515–528 (Haer Institute, New Brunswick, 1981).

  104. 104.

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

  105. 105.

    & Nucleus accumbens dopamine depletions make rats more sensitive to high ratio requirements but do not impair primary food reinforcement. Neuroscience 92, 545–552 (1999).

  106. 106.

    , & Destruction of dopaminergic nerve terminals in nucleus accumbens: effect on D-amphetamine self-administration. Pharmacol. Biochem. Behav. 11, 553–556 (1979).

  107. 107.

    , , & Increases in food intake or food-seeking behavior induced by GABAergic, opioid, or dopaminergic stimulation of the nucleus accumbens: is it hunger? Psychopharmacology 172, 241–247 (2004).

  108. 108.

    & Striatal regulation of morphine-induced hyperphagia: an anatomical mapping study. Psychopharmacology 111, 207–214 (1993).

  109. 109.

    Reinforcing effects of morphine in the nucleus accumbens. Brain Res. 237, 429–440 (1982).

  110. 110.

    & Self-administration of D-ala2-met-enkephalinamide at hypothalamic self-stimulation sites. Brain Res. 194, 155–170 (1980).

  111. 111.

    , & Self-administration of methionine enkephalin into the nucleus accumbens. Pharmacol. Biochem. Behav. 20, 451–455 (1984).

  112. 112.

    et al. Self-injection of amphetamine directly into the brain. Psychopharmacology 81, 158–163 (1983).

  113. 113.

    , & Bilateral intra-accumbens self-administration of D-amphetamine: antagonism with intra-accumbens SCH-23390 and sulpiride. Psychopharmacology 114, 477–485 (1994).

  114. 114.

    , & Habit-forming actions of nomifensine in nucleus accumbens. Psychopharmacology (Berl.) 122, 194–197 (1995).

  115. 115.

    & The cerebral ventricles as the avenue for the dipsogenic action of intracranial angiotensin. Brain Res. 86, 399–418 (1975). The potential for migration of centrally administered drugs to and through the ventricular system is nicely illustrated in this classic paper.

  116. 116.

    & Intracranial self-administration of morphine into the ventral tegmental area in rats. Life Sci. 28, 551–555 (1981).

  117. 117.

    & Microinjections of phencyclidine (PCP) and related drugs into nucleus accumbens shell potentiate lateral hypothalamic brain stimulation reward. Psychopharmacology 128, 413–420 (1996).

  118. 118.

    & Cortical dopaminergic involvement in cocaine reinforcement. Science 221, 773–775 (1983).

  119. 119.

    Involvement of the olfactory tubercle in cocaine reward: intracranial self-administration studies. J. Neurosci. 23, 9305–9511 (2003).

  120. 120.

    & A psychomotor stimulant theory of addiction. Psychol. Rev. 94, 469–492 (1987).

  121. 121.

    & Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc. Natl Acad. Sci. USA 85, 5274–5278 (1988).

  122. 122.

    , , & Neurobiology of motivation: double dissociation of two motivational mechanisms mediating opiate reward in drug-naive versus drug-dependent rats. Behav. Neurosci. 106, 798–807 (1992).

  123. 123.

    & Blockade of mesolimbic dopamine transmission dramatically increases sensitivity to the rewarding effects of nicotine in the ventral tegmental area. Mol. Psychiatry 8, 50–59 (2003).

  124. 124.

    The neurobiology of craving: implications for the understanding and treatment of addiction. J. Abnorm. Psychol. 97, 118–132 (1988).

  125. 125.

    , & Studies on the distinction between uptake inhibition and release of (3H)dopamine in rat brain tissue slices. Biochem. Pharmacol. 24, 847–852 (1975).

  126. 126.

    , , & Cocaine receptors on dopamine transporters are related to self-administration of cocaine. Science 237, 1219–1223 (1987).

  127. 127.

    et al. Cocaine self-administration in dopamine-transporter knockout mice. Nature Neurosci. 1, 132–137 (1998).

  128. 128.

    et al. Cocaine reward models: conditioned place preference can be established in dopamine- and in serotonin-transporter knockout mice. Proc. Natl Acad. Sci. USA 95, 699–704 (1998).

  129. 129.

    , , , & Dopamine uptake through the norepinephrine transporter in brain regions with low levels of the dopamine transporter: evidence from knock-out mouse lines. J. Neurosci. 22, 389–395 (2002).

  130. 130.

    et al. Cocaine and amphetamine increase extracellular dopamine in the nucleus accumbens of mice lacking the dopamine transporter gene. J. Neurosci. 21, 1–4 (2001).

  131. 131.

    et al. Molecular mechanisms of cocaine reward: combined dopamine and serotonin transporter knockouts eliminate cocaine place preference. Proc. Natl Acad. Sci. USA 98, 5300–5305 (2001).

  132. 132.

    & Break-points on a progressive ratio schedule reinforced by intravenous cocaine increase following depletion of forebrain serotonin. Psychopharmacology 101, 262–266 (1990).

  133. 133.

    , & Increased self-administration of D-amphetamine after destruction of 5-hydroxytryptaminergic nerves. Pharmacol. Biochem. Behav. 12, 937–941 (1981).

  134. 134.

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

  135. 135.

    & Parsing reward. Trends Neurosci. 26, 507–513 (2003).

  136. 136.

    & The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res. Reviews 18, 247–292 (1993).

  137. 137.

    & Neuronal coding of prediction errors. Ann. Rev. Neurosci. 23, 473–500 (2000).

  138. 138.

    & A predictive reinforcement model of dopamine neurons for learning approach behavior. J. Comput. Neurosci. 6, 191–214 (1999).

  139. 139.

    & Dopamine neurons of the monkey midbrain: contingencies of responses to active touch during self-initiated arm movements. J. Neurophysiol. 63, 592–606 (1990).

  140. 140.

    , , & Neuronal activity in monkey ventral striatum related to the expectation of reward. J. Neurosci. 12, 4595–4610 (1992).

  141. 141.

    Brain reward circuitry: insights from unsensed incentives. Neuron 36, 229–240 (2002).

  142. 142.

    The acquisition of responding with conditioned reinforcement: effects of pipradrol, methylphenidate, D-amphetamine and nomifensine. Psychopharmacology 58, 79–87 (1978).

  143. 143.

    & Specific hungers and poison avoidance as adaptive specializations of learning. Psychol. Rev. 78, 459–486 (1971).

  144. 144.

    Effets des administrations post-prandiales de glucose sur l'etablissement des appétits. C. R. Seances Soc. Biol. Fil. 158, 212–215 (1959).

  145. 145.

    & Conditioned enhancement of flavor evaluation reinforced by intragastric glucose. II. Taste reactivity analysis. Physiol. Behav. 74, 495–505 (2001).

  146. 146.

    & Contingent and non-contingent actions of sucrose and saccharin reinforcers: effects on taste preference and memory. Physiol. Behav. 32, 195–203 (1984).

  147. 147.

    & Differential control over drug-seeking behavior by drug-associated conditioned reinforcers and discriminative stimuli predictive of drug availability. Behav. Neurosci. 117, 952–960 (2003).

  148. 148.

    , & Evidence that appetitive responses for dehydration and food-deprivation are learned. Physiol. Behav. 75, 295–304 (2002).

  149. 149.

    , & Developmental changes in suckling of rat pups. Nature 258, 318–320 (1975).

  150. 150.

    & Appetitive learning in 1-day-old rat pups. Science 205, 419–421 (1979).

  151. 151.

    Instrumental performance following a shift in primary motivation depends on incentive learning. J. Exp. Psychol. Anim. Behav. Process. 18, 236–250 (1992).

  152. 152.

    Reinforcement as consolidation. Psychol. Rev. 76, 82–96 (1969).

  153. 153.

    Parsimonious biological models of memory and reinforcement. Psychol. Rev. 76, 70–81 (1969).

  154. 154.

    , & Facilitation of learning by reward of post-trial memory processes. Experietia 30, 1038–1040 (1974).

  155. 155.

    The molecular biology of memory storage: a dialogue between genes and synapses. Science 294, 1030–1038 (2001).

  156. 156.

    , & Dopaminergic antagonists prevent long-term maintenance of posttetanic LTP in the CA1 region of rat hippocampal slices. Brain Res. 522, 69–75 (1990).

  157. 157.

    , , & The effect of dopaminergic D1 receptor blockade during tetanization on the expression of long-term potentiation in the rat CA1 region in vitro. Neurosci. Lett. 129, 111–114 (1991).

  158. 158.

    , , & Dopamine-dependent facilitation of LTP induction in hippocampal CA1 by exposure to spatial novelty. Nature Neurosci. 6, 526–531 (2003).

  159. 159.

    et al. A double dissociation within the hippocampus of dopamine D1/D5 receptor and β-adrenergic receptor contributions to the persistence of long-term potentiation. Neuroscience 92, 485–497 (1999).

  160. 160.

    & D1/D5 dopamine receptors inhibit depotentiation at CA1 synapses via cAMP-dependent mechanism. J. Neurosci. 18, 1270–1279 (1998).

  161. 161.

    et al. Roles of dopamine receptors in long-term depression: enhancement via D1 receptors and inhibition via D2 receptors. Recept. Channels 4, 1–8 (1996).

  162. 162.

    , , , & Long-term synaptic depression in the striatum: physiological and pharmacological characterization. J. Neurosci. 12, 4224–4233 (1992).

  163. 163.

    , , , & Dopaminergic control of synaptic plasticity in the dorsal striatum. Eur. J. Neurosci. 13, 1071–1077 (2001).

  164. 164.

    , & Dopamine gates LTP induction in lateral amygdala by suppressing feedforward inhibition. Nature Neurosci. 6, 587–592 (2003).

  165. 165.

    , , & Genetic evidence for the bidirectional modulation of synaptic plasticity in the prefrontal cortex by D1 receptors. Proc. Natl Acad. Sci. USA 101, 3236–3241 (2004).

  166. 166.

    , , & Dopaminergic modulation of long-term synaptic plasticity in rat prefrontal neurons. Cereb. Cortex 13, 1251–1256 (2003).

  167. 167.

    , & Dopamine favours the emergence of long-term depression versus long-term potentiation in slices of rat prefrontal cortex. Neurosci. Lett. 188, 125–128 (1995).

  168. 168.

    , , & Synaptic plasticity in an in vitro slice preparation of the rat nucleus accumbens. Eur. J. Neurosci. 5, 107–117 (1993).

  169. 169.

    & Simultaneous LTP of non-NMDA- and LTD of NMDA-receptor-mediated responses in the nucleus accumbens. Nature 368, 242–246 (1994).

  170. 170.

    , , & Long-term potentiation at excitatory amino acid synapses on midbrain dopamine neurons. Neuroreport 10, 221–226 (1999).

  171. 171.

    & Properties and plasticity of excitatory synapses on dopaminergic and GABAergic cells in the ventral tegmental area. J. Neurosci. 19, 3723–3730 (1999).

  172. 172.

    , & Modulation of long-term depression by dopamine in the mesolimbic system. J. Neurosci. 20, 5581–5586 (2000).

  173. 173.

    , , & Drugs of abuse and stress trigger a common synaptic adaptation in dopamine neurons. Neuron 37, 577–582 (2003).

  174. 174.

    & Localized intracaudate dopamine D2 receptor activation during the post-training period improves memory for visual or olfactory conditioned emotional responses in rats. Behav. Neural Biol. 55, 255–269 (1991). This paper shows that dopamine enhances memory consolidation involving different sensory modalities in different portions of the striatum.

  175. 175.

    , & Amygdala modulation of hippocampal-dependent and caudate nucleus-dependent memory processes. Proc. Natl Acad. Sci. USA 91, 8477–8481 (1994).

  176. 176.

    & Double dissociation of the behavioural effects of R(+) 7-OH-DPAT infusions in the central and basolateral amygdala nuclei upon Pavlovian and instrumental conditioned appetitive behaviours. Psychopharmacology 140, 458–469 (1998).

  177. 177.

    Drug-activation of brain reward pathways. Drug Alcohol Depend. 51, 13–22 (1998).

  178. 178.

    , , & Anatomical substrates for glutamate-dopamine interactions: evidence for specificity of connections and extrasynaptic actions. Ann. NY Acad. Sci. 1003, 36–52 (2003).

  179. 179.

    , , & Electrical stimulation of the prefrontal cortex increases cholecystokinin, glutamate, and dopamine release in the nucleus accumbens: an in vivo microdialysis study in freely moving rats. J. Neurosci. 18, 6492–6500 (1998).

  180. 180.

    & Intracranial cocaine self-administration into the medial prefrontal cortex increases dopamine turnover in the nucleus accumbens. J. Pharmacol. Exp. Ther. 265, 592–600 (1993).

  181. 181.

    & Modulation of memory fields by dopamine D1 receptors in prefrontal cortex. Nature 376, 572–575 (1995).

  182. 182.

    & The circuitry mediating cocaine-induced reinstatement of drug-seeking behavior. J. Neurosci. 21, 8655–8663 (2001).

  183. 183.

    , & Prefrontal glutamate release into the core of the nucleus accumbens mediates cocaine-induced reinstatement of drug-seeking behavior. J. Neurosci. 23, 3531–3537 (2003).

  184. 184.

    , , & A role for the prefrontal cortex in stress- and cocaine-induced reinstatement of cocaine seeking in rats. Psychopharmacology 168, 66–74 (2003).

  185. 185.

    , , , & Manipulation of dopamine d1-like receptor activation in the rat medial prefrontal cortex alters stress- and cocaine-induced reinstatement of conditioned place preference behavior. Neuroscience 119, 497–505 (2003).

  186. 186.

    , & Involvement of the amygdala in stimulus-reward associations: interaction with the ventral striatum. Neuroscience 30, 77–86 (1989).

  187. 187.

    , , & Excitotoxic lesions of the basolateral amygdala impair the acquisition of cocaine-seeking behaviour under a second-order schedule of reinforcement. Psychopharmacology 127, 213–224 (1996).

  188. 188.

    , , , & Involvement of the central nucleus of the amygdala and nucleus accumbens core in mediating Pavlovian influences on instrumental behaviour. Eur. J. Neurosci. 13, 1984–1992 (2001).

  189. 189.

    , , , & Lesions of the orbitofrontal but not medial prefrontal cortex disrupt conditioned reinforcement in primates. J. Neurosci. 23, 11189–11201 (2003).

  190. 190.

    & The effects of selective orbitofrontal cortex lesions on the acquisition and performance of cue-controlled cocaine seeking in rats. Ann. NY Acad. Sci. 1003, 410–411 (2003).

  191. 191.

    , , & Encoding predicted outcome and acquired value in orbitofrontal cortex during cue sampling depends upon input from basolateral amygdala. Neuron 39, 855–867 (2003).

  192. 192.

    & Brain stimulation reward and dopamine terminal fields. I. Caudate-putamen, nucleus accumbens and amygdala. Brain Res. 297, 265–273 (1984).

  193. 193.

    , & Self-stimulation of hippocampus in rats. J. Comp. Physiol. Psychol. 61, 353–359 (1966).

  194. 194.

    , & Intracerebral self-administration of amphetamine by rhesus monkeys. Neurosci. Lett. 24, 81–86 (1981).

  195. 195.

    , & Hippocampal μ-receptors mediate opioid reinforcement in the CA3 region. Brain Res. 545, 8–16 (1991).

  196. 196.

    & Catecholamine innervation of the basal forebrain. IV. Topography of the dopamine projection to the basal forebrain and neostriatum. J. Comp. Neurol. 180, 545–580 (1978). This classic paper first characterized the midbrain dopamine system as a single system with topologically graded projections rather than a set of independent, non-overlapping systems. This anatomical perspective is fundamental to the suggestion that dopamine plays similar parts in various of its projection fields.

  197. 197.

    , & in The Rat Nervous System (ed. Paxinos, G.) 579–628 (Academic, New York, 1995).

  198. 198.

    , , & Dopamine release in the dorsal striatum during cocaine-seeking behavior under the control of drug-associated cue. J. Neurosci. 22, 6247–6253 (2002).

Download references

Acknowledgements

I thank Y. Shaham, B. Hoffer, S. Ikemoto and A. Zangen for critical comments on an earlier draft.

Author information

Affiliations

  1. Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Bethesda, Maryland 20892, USA.  rwise@intra.nida.nih.gov

    • Roy A. Wise

Authors

  1. Search for Roy A. Wise in:

Competing interests

The author declares no competing financial interests.

Glossary

NEUROLEPTIC

A drug that blocks the effects of dopamine by binding to and occluding the dopamine receptor.

REINFORCEMENT

The strengthening of stimulus–stimulus, stimulus–response or response–reward associations that results from the timely presentation of a reward. The term applies to both Pavlovian and instrumental conditioning, though it is most frequently used with the latter.

REWARD

In the noun form (a reward), an object or event that elicits approach and is worked for; its analogue is 'a reinforcer'. In the verb form (to reward) the term is synonymous with 'to reinforce'. As a verb it is used with respect to instrumental but not Pavlovian conditioning.

DRIVE

The energizing effects on behaviour of internal stimuli associated with tissue need or hormonal level, or of external stimuli associated with past rewards ('incentive motivational' stimuli).

PRIMING

The precipitation of a learned response habit by administration of an unearned sample of the reward.

SUBSTANTIA NIGRA

Originally named for the pigmented dopamine cells of zona compacta of the substantia nigra (SNc) and ventral tegmental area, the term now designates only the lateral portion of the dopamine cells: those that project to the caudate–putamen. The term has also been extended to include the group of non-pigmented (γ-aminobutyric acid-mediated) substantia nigra pars reticulata (SNr) cells that lies ventral to the SNc and that provides feedback to it.

STRIATUM

In the rat the multiple bundles of the internal capsule give the caudate–putamen and the nucleus accumbens a striated appearance in sagittal section. For this reason they have come to be known as the dorsal and ventral striatum, respectively. The olfactory tubercle, beneath nucleus accumbens, has been recognized as an extension of the ventral striatum.

About this article

Publication history

Published

DOI

https://doi.org/10.1038/nrn1406

Further reading