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Reward, Motivation, Cognition: Psychobiology of Mesotelencephalic Dopamine Systems

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Abstract

The sections in this article are:

1 Organization and Regulation of Mesolimbic DA System
1.1 Anatomy
1.2 Chemistry
1.3 Physiology
2 Motor Functions
2.1 Regional Considerations
2.2 Stereotypy
2.3 Biochemical Anatomy of Mesolimbic Motor System
2.4 Rotation
2.5 Theoretical Implications
3 Dopaminergic Substrates of Reward
3.1 Intracranial Self‐Stimulation
3.2 Intravenous Self‐Administration
3.3 Place‐Preference Conditioning
3.4 Functional Significance
4 Adjunctive Behaviors
4.1 Electrical Stimulation of Lateral Hypothalamus
4.2 Tail Pinch‐Induced Behaviors
5 Learning, Memory, and Cognition
6 Possible Role of Mesotelencephalic DA Systems in Motivation and Emotion
Figure 1. Figure 1.

A–F: frontal sections of rat mesencephalon. Asterisks, location of perikarya in substantia nigra, zona compacta (snc) and ventral tegmental area that contain both cholecystokinin (CCK) and dopamine (DA). Ascending DA‐containing fibers and fibers containing both DA and CCK are also indicated, abp, Nucleus amygdaloideus basalis posterior; al, n. amygdaloideus lateralis; amp, n. amygdaloideus medialis posterior; apo, n. amygdaloideus posterior; at, n. anteromedialis thalami; c, n. caudatus putamen; CAE, capsula externa; CC, crus cerebri; CP, posterior commissure; DT, decussationes tegmenti; F, fornix; FH, fimbria hippocampi; FLM, fasciculus longitudinalis medialis; FMT, f. mammillothalamicus; FR, f. retroflexus; HI, hippocampus; hI, habenula lateralis; hm, habenula medialis; ip, n. interpeduncularis; LM, lemniscus medialis; mcgm, n. marginalis corporis geniculati medialis; MFB, medial forebrain bundle; nIII, oculomotor nerve; na, n. arcuatus; ncu, n. cuneiformis; nhp, n. hypothalamicus posterior; nl, n. lateralis; nml, nucleus mammillaris lateralis; nmm, n. mammillaris medialis; PCMA, pedunculus corporis mammillaris; pi, piriform cortex; pv, n. periventricularis thalami; r, n. ruber; SGC, substantia grisea centralis; snl, substantia nigra, pars lateralis; snr, substantia nigra, zona reticulata; ST, stria terminalis; SUM, decussatio supramammillaris; sut, n. subthal‐amicus; and zi, zona incerta.

From Hökfelt et al. 114, © 1980, with permission from Pergamon Press, Ltd
Figure 2. Figure 2.

Relationship between enkephalin‐containing fibers (stippling) and DA‐containing perikarya in the substantia nigra, zona compacta (SNC) and ventral tegmental area (VTA; open circles) of rat mesencephalon, cc, Crus cerebri; H1 and H2, fields of Forel; MB, mammillary body; ru, n. ruber; SNL, substantia nigra, pars lateralis; SNR, substantia nigra, zona reticulata; Vm, 3rd ventricle; and Zi, zona incerta.

From Johnson et al. 125
Figure 3. Figure 3.

A: dose‐related attenuation by haloperidol (Hal) of place‐preference conditioning produced by unilateral microinjection of (D‐Ala2)Met5‐enkephalinamide (D‐Ala, 200 ng) into VTA. Rats were habituated to shuttlebox and time spent in each compartment was measured prior to drug injections. Conditioning procedure involved pairing distinctive environmental stimuli in initially nonpreferred compartment with D‐Ala injections for 30 min/day on 3 consecutive days. Place‐preference conditioning was assessed on subsequent drug‐free test day and is expressed as increase in percentage of time spent in compartment paired with D‐Ala treatment. Veh, vehicle. B: blockade of place‐preference conditioning produced by unilateral microinjections of D‐Ala (200 ng) into VTA by prior ipsilateral 6‐hydroxydopamine (6‐OHDA) lesions of mesotelencephalic DA projections at level of lateral hypothalamus. Identical 6‐OHDA lesions contralateral to VTA injections of D‐Ala did not interfere with place‐preference conditioning. Ipsilateral and contralateral 6‐OHDA lesions reduced forebrain DA concentrations to <5% of control levels. Both experiments implicate mesotelencephalic DA systems in reinforcing properties of injections of this enkephalin analogue into VTA.



Figure 1.

A–F: frontal sections of rat mesencephalon. Asterisks, location of perikarya in substantia nigra, zona compacta (snc) and ventral tegmental area that contain both cholecystokinin (CCK) and dopamine (DA). Ascending DA‐containing fibers and fibers containing both DA and CCK are also indicated, abp, Nucleus amygdaloideus basalis posterior; al, n. amygdaloideus lateralis; amp, n. amygdaloideus medialis posterior; apo, n. amygdaloideus posterior; at, n. anteromedialis thalami; c, n. caudatus putamen; CAE, capsula externa; CC, crus cerebri; CP, posterior commissure; DT, decussationes tegmenti; F, fornix; FH, fimbria hippocampi; FLM, fasciculus longitudinalis medialis; FMT, f. mammillothalamicus; FR, f. retroflexus; HI, hippocampus; hI, habenula lateralis; hm, habenula medialis; ip, n. interpeduncularis; LM, lemniscus medialis; mcgm, n. marginalis corporis geniculati medialis; MFB, medial forebrain bundle; nIII, oculomotor nerve; na, n. arcuatus; ncu, n. cuneiformis; nhp, n. hypothalamicus posterior; nl, n. lateralis; nml, nucleus mammillaris lateralis; nmm, n. mammillaris medialis; PCMA, pedunculus corporis mammillaris; pi, piriform cortex; pv, n. periventricularis thalami; r, n. ruber; SGC, substantia grisea centralis; snl, substantia nigra, pars lateralis; snr, substantia nigra, zona reticulata; ST, stria terminalis; SUM, decussatio supramammillaris; sut, n. subthal‐amicus; and zi, zona incerta.

From Hökfelt et al. 114, © 1980, with permission from Pergamon Press, Ltd


Figure 2.

Relationship between enkephalin‐containing fibers (stippling) and DA‐containing perikarya in the substantia nigra, zona compacta (SNC) and ventral tegmental area (VTA; open circles) of rat mesencephalon, cc, Crus cerebri; H1 and H2, fields of Forel; MB, mammillary body; ru, n. ruber; SNL, substantia nigra, pars lateralis; SNR, substantia nigra, zona reticulata; Vm, 3rd ventricle; and Zi, zona incerta.

From Johnson et al. 125


Figure 3.

A: dose‐related attenuation by haloperidol (Hal) of place‐preference conditioning produced by unilateral microinjection of (D‐Ala2)Met5‐enkephalinamide (D‐Ala, 200 ng) into VTA. Rats were habituated to shuttlebox and time spent in each compartment was measured prior to drug injections. Conditioning procedure involved pairing distinctive environmental stimuli in initially nonpreferred compartment with D‐Ala injections for 30 min/day on 3 consecutive days. Place‐preference conditioning was assessed on subsequent drug‐free test day and is expressed as increase in percentage of time spent in compartment paired with D‐Ala treatment. Veh, vehicle. B: blockade of place‐preference conditioning produced by unilateral microinjections of D‐Ala (200 ng) into VTA by prior ipsilateral 6‐hydroxydopamine (6‐OHDA) lesions of mesotelencephalic DA projections at level of lateral hypothalamus. Identical 6‐OHDA lesions contralateral to VTA injections of D‐Ala did not interfere with place‐preference conditioning. Ipsilateral and contralateral 6‐OHDA lesions reduced forebrain DA concentrations to <5% of control levels. Both experiments implicate mesotelencephalic DA systems in reinforcing properties of injections of this enkephalin analogue into VTA.

References
 1. Adams, W. J., S. A. Lorens, and C. L. Mitchell. Morphine enhances lateral hypothalamic self‐stimulation in the rat. Proc. Soc. Exp. Biol. Med. 140: 770–771, 1972.
 2. Adler, M. W. Changes in sensitivity to amphetamine in rats with chronic brain lesions. J. Pharmacol. Exp. Ther. 134: 214–221, 1961.
 3. Aghajanian, G. K., and B. S. Bunney. Central dopaminergic neurons: neurophysiological identification and responses to drugs. In: Frontiers in Catecholamine Research, edited by S. H. Snyder and E. Usdin. New York: Pergamon, 1973, p. 643–648.
 4. Agnati, L. F., K. Fuxe, K. Andersson, F. Benfenati, P. Cortelli, and R. D'Alessandro. The mesolimbic dopamine system: evidence for a high amine turnover and for a heterogeneity of the dopamine neuron population. Neurosci. Lett. 18: 45–51, 1980.
 5. Andén, N. E., S. G. Butcher, H. Corrodi, K. Fuxe, and U. Ungerstedt. Receptor activity and turnover of dopamine and noradrenaline after neuroleptics. Eur. J. Pharmacol. 11: 303–314, 1970.
 6. Andén, N. E., and G. Stock. Effect of clozapine on the turnover of dopamine in the corpus striatum and in the limbic system. J. Pharm. Pharmacol. 25: 346–348, 1973.
 7. Angrist, B. M., B. Shopsin, and S. Gershon. Comparative psychotomimetic effects of stereoisomers of amphetamine. Nature London 234: 152–153, 1971.
 8. Antelman, S. M., N. E. Rowland, and A. E. Fisher. Stimulation bound ingestive behavior: a view from the tail. Physiol. Behav. 17: 743–748, 1976.
 9. Antelman, S. M., H. Szechtman, P. Chin, and A. E. Fisher. Tail pinch‐induced eating, gnawing and licking behavior in rats: dependence on the nigro‐striatal dopamine system. Brain Res. 99: 319–337, 1975.
 10. Argiolas, A., F. Fadda, M. R. Melis, and G. L. Gessa. Haloperidol increases DOPAC in the substantia nigra but not in the ventral tegmental area. Life Sci. 24: 2279–2284, 1979.
 11. Argiolas, A., F. Fadda, M. R. Melis, and G. L. Gessa. Differential effect of haloperidol on DOPAC levels in the substantia nigra and ventral tegmental area. Pharmacol. Res. Commun. 12: 683–688, 1980.
 12. Asher, I. M., and G. K. Aghajanian. 6‐Hydroxydopamine lesions of olfactory tubercles and caudate nuclei: effect on amphetamine‐induced stereotyped behavior in rats. Brain Res. 82: 1–12, 1974.
 13. Bacopoulos, N. G., and R. H. Roth. Apomorphine‐haloper‐idol interactions: different types of antagonism in cortical and subcortical brain regions. Brain Res. 205: 313–319, 1981.
 14. Bacotti, A. V., and J. E. Barrett. Effect of chlordiazepoxide on schedule‐controlled responding and schedule‐induced drinking. Pharmacol. Biochem. Behav. 4: 299–304, 1976.
 15. Bannon, M. J., R. L. Michaud, and R. H. Roth. Mesocortical dopamine neurons. Lack of autoreceptors modulating dopamine synthesis. Mol. Pharmacol. 19: 270–275, 1981.
 16. Barrett, J. E., and E. S. Weinberg. Effects of chlordiazepoxide on schedule‐induced water and alcohol consumption in the squirrel monkey. Psychopharmacologia 40: 319–328, 1975.
 17. Bartholini, G. Differential effect of neuroleptic drugs on dopamine turnover in the extrapyramidal and limbic system. J. Pharm. Pharmacol. 28: 429–433, 1976.
 18. Bartholini, G., H. H. Keller, and A. Pletscher. Drug‐induced changes of dopamine turnover in striatum and limbic system of the rat. J. Pharm. Pharmacol. 27: 439–442, 1975.
 19. Bartus, R. T. Short‐term memory in the rhesus monkey: effects of dopamine blockade via acute haloperidol administration. Pharmacol. Biochem. Behav. 9: 353–357, 1978.
 20. Beckstead, R. M., V. B. Domesick, and W. J. H. Nauta. Efferent connections of the substantia nigra and ventral tegmental area in the rat. Brain Res. 175: 191–217, 1979.
 21. Beninger, R. J., D. R. Hanson, and A. G. Phillips. The acquisition of responding with conditioned reinforcement: effects of cocaine, (+)‐amphetamine and pipradrol. Br. J. Pharmacol. 74: 149–154, 1981.
 22. Beninger, R. J., A. J. MacLennan, and J. P. J. Pinel. The use of conditioned defensive burying to test the effects of pimozide on associative learning. Pharmacol. Biochem. Behav. 12: 445–448, 1980.
 23. Beninger, R. J., S. T. Mason, A. G. Phillips, and H. C. Fibiger. The use of conditioned suppression to evaluate the nature of neuroleptic‐induced avoidance deficits. J. Pharmacol. Exp. Ther. 213: 623–627, 1980.
 24. Beninger, R. J., S. T. Mason, A. G. Phillips, and H. C. Fibiger. The use of extinction to investigate the nature of neuroleptic‐induced avoidance deficits. Psychopharmacology 69: 11–18, 1980.
 25. Beninger, R. J., and A. G. Phillips. The effect of pimozide on the establishment of conditioned reinforcement. Psycho‐pharmacology 68: 147–153, 1980.
 26. Bindra, D. Neuropsychological interpretation of the effects of drive and incentive‐motivation on general activity and instrumental behavior. Psychol. Rev. 75: 1–22, 1968.
 27. Björklund, A., and O. Lindvall. The mesotelencephalic dopamine neuron system: a review of its anatomy. In: Limbic Mechanisms, edited by K. E. Livingston and O. Hornykiewicz. New York: Plenum, 1978, p. 307–331.
 28. Bolles, R. C. Reinforcement, expectancy, and learning. Psychol. Rev. 79: 394–409, 1972.
 29. Bowers, M. B., and A. Rozitis. Regional differences in homovanillic acid concentrations after acute and chronic administration of antipsychotic drugs. J. Pharm. Pharmacol. 26: 743–745, 1974.
 30. Bozarth, M. A., and R. W. Wise. Heroin reward is dependent on a dopaminergic substrate. Life Sci. 29: 1881–1886, 1981.
 31. Brand, S., and P. Rakic. Neurogenesis of the nucleus accumbens septi and neighboring septal nuclei in the rhesus monkey: a combined [3H]thymidine and electron microscopic study. Neuroscience 5: 2125–2138, 1980.
 32. Breese, G. R., B. R. Cooper, and R. A. Mueller. Evidence for involvement of 5‐hydroxytryptamine in the actions of amphetamine. Br. J. Pharmacol. 52: 307–314, 1974.
 33. Broekkamp, C. L. E., and A. G. Phillips. Stimulant effects of enkephalin microinjection into the dopaminergic A10 area. Nature London 278: 560–562, 1979.
 34. Broekkamp, C. L. E., A. G. Phillips, and A. R. Cools. Facilitation of self‐stimulation behaviour following intracerebral microinjection of opioids into the ventral tegmental area. Pharmacol. Biochem. Behav. 11: 289–295, 1979.
 35. Broekkamp, C. L. E., J. H. Van Den Bogaard, H. J. Heijnen, R. H. Rops, A. R. Cools, and J. M. Van Rossum. Separation of inhibiting and stimulating effects of morphine on self‐stimulation behaviour by intracerebral microinjections. Eur. J. Pharmacol. 36: 443–446, 1976.
 36. Broekkamp, C. L. E., P. A. M. Van Dongen, and J. M. Van Rossum. Neostriatal involvement in reinforcement and motivation. In: Psychobiology of the Striatum, edited by A. R. Cools, A. H. M. Lohman, and J. H. L. Van Den Bercken. Amsterdam: North‐Holland, 1977, p. 61–72.
 37. Broekkamp, C. L. E., and J. M. Van Rossum. The effect of microinjections of morphine and haloperidol into the neostriatum and the nucleus accumbens on self‐stimulation behavior. Arch. Int. Pharmacodyn. Ther. 217: 110–117, 1975.
 38. Browder, S., D. C. German, and P. A. Shore. Midbrain dopamine neurons: differential responses to amphetamine isomers. Brain Res. 207: 333–342, 1981.
 39. Brozoski, T. J., R. M. Brown, H. E. Rosvold, and P. S. Goldman. Cognitive deficit caused by regional depletion of dopamine in prefrontal cortex of rhesus monkey. Science 205: 929–932, 1979.
 40. Bunney, B. S. Central dopaminergic systems: two in vivo electrophysiological models for predicting therapeutic efficacy and neurological side effects of putative antipsychotic drugs. In: Animal Models in Psychiatry and Neurology, edited by I. Hanin and E. Usdin. New York: Pergamon, 1977, p. 91–105.
 41. Bunney, B. S., and G. K. Aghajanian. d‐Amphetamine‐induced inhibition of central dopaminergic neurons: mediation by a striatonigral feedback pathway. Science 192: 391–393, 1976.
 42. Bunney, B. S., and G. K. Aghajanian. d‐Amphetamine‐induced depression of central dopamine neurons: evidence for mediation by both autoreceptors and a striato‐nigral feedback pathway. Naunyn‐Schmiedeberg's Arch. Pharmacol. 304: 255–261, 1978.
 43. Bunney, B. S., G. K. Aghajanian, and R. H. Roth. Comparison of effects of L‐dopa, amphetamine and apomorphine on firing rate of rat dopaminergic neurones. Nature London 245: 123–125, 1973.
 44. Bunney, B. S., and A. A. Grace. Acute and chronic haloperidol treatment: comparison of effects on nigral dopaminergic cell activity. Life Sci. 23: 1715–1728, 1978.
 45. Bunney, B. S., J. R. Walters, M. J. Kuhar, R. H. Roth, and G. K. Aghajanian. d‐ and l‐Amphetamine stereoisomers: comparative potencies in affecting the firing of central dopaminergic and noradrenergic neurons. Psychopharmacol. Commun. 1: 177–190, 1975.
 46. Campbell, B. A., P. Ballantine, and G. Lynch. Hippocampal control of behavioral arousal: duration of lesion effects and possible interactions with recovery after frontal cortical damage. Exp. Neurol. 33: 159–170, 1971.
 47. Carlsson, A., and M. Lindqvist. Effect of chlorpromazine and haloperidol on formation of 3‐methoxytyramine and normetanephrine in mouse brain. Acta Pharmacol. Toxicol. 20: 140–144, 1963.
 48. Carter, C. J., and C. J. Pycock. Behavioral and biochemical effects of dopamine and noradrenaline depletion within the medial prefrontal cortex of the rat. Brain Res. 192: 163–176, 1980.
 49. Carter, D. A., and H. C. Fibiger. Ascending projections of presumed dopamine‐containing neurons in the ventral tegmentum of the rat as demonstrated by horseradish peroxidase. Neuroscience 2: 569–576, 1977.
 50. Cheramy, A., V. Leviel, and J. Glowinski. Dendritic release of dopamine in the substantia nigra. Nature London 289: 537–542, 1981.
 51. Chiodo, L. A., S. M. Antelman, A. R. Caggiula, and C. G. Lineberry. Sensory stimuli alter the discharge rate of dopamine (DA) neurons: evidence for two functional types of DA cells in the substantia nigra. Brain Res. 189: 544–549, 1980.
 52. Chiueh, C. C., and K. E. Moore. d‐Amphetamine‐induced release of “newly synthesized” and “stored” dopamine from the caudate nucleus in vivo. J. Pharmacol. Exp. Ther. 192: 642–653, 1975.
 53. Clavier, R. M., and M. E. Corcoran. Attenuation of self‐stimulation from substantia nigra but not dorsal tegmental noradrenergic bundle by lesions of sulcal prefrontal cortex. Brain Res. 113: 59–69, 1976.
 54. Clavier, R. M., and H. C. Fibiger. On the role of ascending catecholaminergic projections in intracranial self‐stimulation of the substantia nigra. Brain Res. 131: 271–286, 1977.
 55. Clavier, R. M., and A. Routtenberg. Ascending mono‐amine‐containing fiber pathways related to intracranial self‐stimulation: histochemical fluorescence study. Brain Res. 72: 25–40, 1974.
 56. Collier, T. J., S. Kurtzman, and A. Routtenberg. Intracranial self‐stimulation derives from entorhinal cortex. Brain Res. 137: 188–196, 1977.
 57. Conrad, L. C. A., and D. W. Pfaff. Autoradiographic tracing of nucleus accumbens efferents in the rat. Brain Res. 113: 589–596, 1976.
 58. Corbett, D., and R. A. Wise. Intracranial self‐stimulation in relation to the ascending dopaminergic systems of the midbrain: a moveable electrode mapping study. Brain Res. 185: 1–15, 1980.
 59. Costall, B., C. D. Marsden, R. J. Naylor, and C. J. Pycock. The relationship between striatal and mesolimbic dopamine dysfunction and the nature of circling response following 6‐hydroxydopamine and electrolytic lesions of the ascending dopamine systems of rat brain. Brain Res. 118: 87–113, 1976.
 60. Costall, B., C. D. Marsden, R. J. Naylor, and C. J. Pycock. Stereotyped behaviour patterns and hyperactivity induced by amphetamine and apomorphine after discrete 6‐hydroxydopamine lesions of extrapyramidal and mesolimbic nuclei. Brain Res. 123: 89–111, 1977.
 61. Creese, I., and S. D. Iversen. The pharmacological and anatomical substrates of the amphetamine response in the rat. Brain Res. 83: 419–436, 1975.
 62. Crow, T. J. Catecholamine‐containing neurones and electrical self‐stimulation. 1. A review of some data. Psychol. Med. 2: 414–421, 1972.
 63. Crow, T. J. A map of the rat mesencephalon for electrical self‐stimulation. Brain Res. 36: 265–273, 1972.
 64. De Wit, H., and R. A. Wise. Blockade of cocaine reinforcement in rats with the dopamine receptor blocker pimozide, but not with the noradrenergic blockers phentolamine and phenoxybenzamine. Can. J. Psychol. 31: 195–203, 1977.
 65. Dresse, A. Importance du système mésencéphalo‐télencéphalique noradrénergique comme substratum anatomique du comportement d'autostimulation. Life Sci. 5: 1003–1014, 1966.
 66. Edmonds, D. E., and C. R. Gallistel. Parametric analysis of brain‐stimulation reward in the rat. III. Effect of performance variables on the reward summation function. J. Comp. Physiol. Psychol. 87: 876–883, 1974.
 67. Edmonds, D. E., and C. R. Gallistel. Reward versus performance in self‐stimulation: electrode‐specific effects of α‐methyl‐p‐tyrosine on reward in the rat. J. Comp. Physiol. Psychol. 91: 962–974, 1977.
 68. Esposito, R. U., W. Faulkner, and C. Kornetsky. Specific modulation of brain stimulation reward by haloperidol. Pharmacol. Biochem. Behav. 10: 937–940, 1979.
 69. Esposito, R. U., and C. Kornetsky. Opioids and rewarding brain stimulation. Neurosci. Biobehav. Rev. 2: 115–122, 1978.
 70. Ettenberg, A., S. A. Cinsavich, and N. White. Performance effects with repeated‐response measures during pimozide‐produced dopamine receptor blockade. Pharmacol. Biochem. Behav. 11: 557–561, 1979.
 71. Ettenberg, A., G. F. Koob, and F. E. Bloom. Response artifact in the measurement of neuroleptic‐induced anhedonia. Science 213: 357–359, 1981.
 72. Fadda, F., A. Argiolas, M. R. Melis, A. H. Tissari, P. L. Onali, and G. L. Gessa. Stress‐induced increase in 3,4‐dihydroxyphenylacetic acid (DOPAC) in the cerebral cortex and in n. accumbens: reversal by diazepam. Life Sci. 23: 2219–2224, 1978.
 73. Falk, J. L. The nature and determinants of adjunctive behavior. Physiol. Behav. 6: 577–588, 1971.
 74. Fallon, J. H. Collateralization of monoamine neurons: mesotelencephalic dopamine projections to caudate, septum, and frontal cortex. J. Neurosci. 12: 1361–1368, 1981.
 75. Fallon, J. H., D. A. Koziell, and R. Y. Moore. Catecholamine innervation of the basal forebrain. II. Amygdala, suprarhinal cortex and entorhinal cortex. J. Comp. Neurol. 180: 509–532, 1978.
 76. Fallon, J. H., and R. Y. Moore. Catecholamine innervation of the basal forebrain. III. Olfactory bulb, anterior olfactory nuclei, olfactory tubercle and piriform cortex. J. Comp. Neurol. 180: 533–544, 1978.
 77. Fallon, J. H., and R. Y. Moore. Catecholamine innervation of the basal forebrain. IV. Topography of the dopamine projection to the basal forebrain and neostriatum. J. Comp. Neurol. 180: 545–579, 1978.
 78. Fallon, J. H., J. N. Riley, and R. Y. Moore. Substantia nigra dopamine neurons: separate populations project to neostriatum and allocortex. Neurosci. Lett. 7: 157–162, 1978.
 79. Ferris, R. M., F. L. M. Tang, and R. A. Maxwell. A comparison of the capacities of isomers of amphetamine, deoxypipradrol and methylphenidate to inhibit the uptake of tritiated catecholamines into rat cerebral cortex slices, synaptosomal preparations of rat cerebral cortex, hypothalamus and striatum and into adrenergic nerves of rabbit aorta. J. Pharmacol. Exp. Ther. 181: 407–416, 1972.
 80. Fibiger, H. C. Drugs and reinforcement: a critical review of the catecholamine theory. Annu. Rev. Pharmacol. Toxicol. 18: 37–56, 1978.
 81. Fibiger, H. C. The organization and some projections of cholinergic neurons of the mammalian forebrain. Brain Res. Rev. 4: 327–388, 1982.
 82. Fibiger, H. C., H. P. Fibiger, and A. Zis. Attenuation of amphetamine induced motor stimulation and stereotypy by 6‐hydroxydopamine in the rat. Br. J. Pharmacol. 47: 683–692, 1973.
 83. Fibiger, H. C., and J. J. Miller. An anatomical and electrophysiological investigation of the serotonergic projection from the dorsal raphe nucleus to the substantia nigra in the rat. Neuroscience 2: 975–987, 1977.
 84. Fibiger, H. C., and A. G. Phillips. Increased intracranial self‐stimulation in rats after long‐term administration of desipramine. Science 214: 683–685, 1981.
 85. Fibiger, H. C., A. G. Phillips, and A. P. Zis. Deficits in instrumental responding after 6‐hydroxydopamine lesions of the nigro‐neostriatal dopaminergic projection. Pharmacol. Biochem. Behav. 2: 87–96, 1974.
 86. Fibiger, H. C., A. P. Zis, and E. G. McGeer. Feeding and drinking deficits after 6‐hydroxydopamine administration in the rat: similarities to the lateral hypothalamic syndrome. Brain Res. 55: 135–148, 1973.
 87. Fibiger, H. C., A. P. Zis, and A. G. Phillips. Haloperidol‐induced disruption of conditioned avoidance responding: attenuation by prior training or by anticholinergic drugs. Eur. J. Pharmacol. 30: 309–314, 1975.
 88. Fink, J. S., and G. P. Smith. Abnormal pattern of amphetamine locomotion after 6‐OHDA lesion of anteromedial caudate. Pharmacol. Biochem. Behav. 11: 23–30, 1979.
 89. Fonnum, F., I. Walaas, and E. Iversen. Localization of GABAergic, cholinergic, and aminergic structures in the mesolimbic system. J. Neurochem. 29: 221–230, 1977.
 90. Ford, R. D., and R. L. Balster. Reinforcing properties of intravenous procaine in rhesus monkeys. Pharmacol. Biochem. Behav. 6: 289–296, 1977.
 91. Fouriezos, G., P. Hansson, and R. A. Wise. Neuroleptic‐induced attenuation of brain stimulation reward in rats. J. Comp. Physiol. Psychol. 92: 661–671, 1978.
 92. Fouriezos, G., and R. A. Wise. Pimozide‐induced extinction of intracranial self‐stimulation: response patterns rule out motor or performance deficits. Brain Res. 103: 377–380, 1976.
 93. Franklin, K. B. J. Catecholamines and self‐stimulation: reward and performance effects dissociated. Pharmacol. Biochem. Behav. 9: 813–820, 1978.
 94. Franklin, K. B. J., and S. N. McCoy. Pimozide‐induced extinction in rats: stimulus control of responding rules out motor deficit. Pharmacol. Biochem. Behav. 11: 71–75, 1979.
 95. Fuxe, K., T. Hökfelt, A. Ljungdahl, L. Agnati, O. Johansson, and M. Perez de la Mora. Evidence for an inhibitory gabaergic control of the mesolimbic dopamine neurons: possibility of improving treatment of schizophrenia by combined treatment with neuroleptics and gabaergic drugs. Med. Biol. 53: 177–183, 1975.
 96. Fuxe, K., T. Hökfelt, and U. Ungerstedt. Localization of indolealkylamines in CNS. Adv. Pharmacol. 6: 235–251, 1968.
 97. Gerber, G. J., J. Sing, and R. W. Wise. Pimozide attenuates lever pressing for water reinforcement in rats. Pharmacol. Biochem. Behav. 14: 201–205, 1981.
 98. Gerfen, C. R., W. A. Staines, G. W. Arbuthnott, and H. C. Fibiger. Crossed connections of the substantia nigra in the rat. J. Comp. Neurol. 207: 283–303, 1982.
 99. German, D. C., and D. M. Bowden. Catecholamine systems at the neural substrate for intracranial self‐stimulation: a hypothesis. Brain. Res. 73: 381–419, 1974.
 100. German, D. C., M. Dalsass, and R. S. Kiser. Electrophysiological examination of the ventral tegmental (A10) area in the rat. Brain Res. 181: 191–197, 1980.
 101. Glickman, S. E., and B. B. Schiff. A biological theory of reinforcement. Psychol. Rev. 74: 81–109, 1967.
 102. Gray, T., and R. A. Wise. Effects of pimozide on lever pressing behavior maintained on an intermittent reinforcement schedule. Pharmacol. Biochem. Behav. 12: 931–935, 1980.
 103. Groves, P. M., C. J. Wilson, and S. J. Young. Self‐inhibition by dopaminergic neurons. Science 190: 522–529, 1975.
 104. Guyenet, P. G., and G. K. Aghajanian. Antidromic identification of dopaminergic and other output neurons of the rat substantia nigra. Brain Res. 150: 69–84, 1978.
 105. Harvey, J. A., and I. Gormezano. Effect of haloperidol and pimozide in classical conditioning of the rabbit nictitating membrane response. J. Pharmacol. Exp. Ther. 218: 712–719, 1981.
 106. Hattori, T., H. C. Fibiger, and P. L. McGeer. Demonstration of a pallidonigral projection innervating dopaminergic neurons. J. Comp. Neurol. 162: 487–504, 1975.
 107. Heffner, T. G., J. A. Hartman, and L. S. Seiden. Feeding increases dopamine metabolism in the rat brain. Science 208: 1168–1170, 1980.
 108. Heikkila, R. E., H. Orlansky, and G. Cohen. Studies on the distinction between uptake inhibition and release of [3H]‐dopamine in rat brain tissue slices. Biochem. Pharmacol. 24: 847–852, 1975.
 109. Heimer, L., R. D. Switzer, and G. W. Van Hoesen. Ventral striatum and ventral pallidum. Components of the motor system? Trends Neurosci. 5: 83–87, 1982.
 110. Hervé, D., H. Simon, G. Blanc, A. Lisoprawski, M. Le Moal, J. Glowinski, and J. P. Tassin. Increased utilization of dopamine in the nucleus accumbens but not in the cerebral cortex after dorsal raphe lesion in the rat. Neurosci. Lett. 15: 127–133, 1979.
 111. Hill, R. T. Facilitation of conditioned reinforcement as a mechanism of psychomotor stimulation. In: Amphetamines and Related Compounds, edited by E. Costa and S. Garattini. New York: Raven, 1970, p. 781–795.
 112. Hoebel, B. G. Feeding and self‐stimulation. Ann. NY Acad. Sci. 157: 758–778, 1969.
 113. Hökfelt, T., J. F. Rehfeld, L. Skirboll, B. Ivemark, M. Goldstein, and K. Markey. Evidence for coexistence of dopamine and CCK in mesolimbic neurones. Nature London 285: 476–478, 1980.
 114. Hökfelt, T., L. Skirboll, J. F. Rehfeld, M. Goldstein, K. Markey, and O. Dann. A subpopulation of mesencephalic dopamine neurons projecting to limbic areas contains a cholecystokinin‐like peptide: evidence from immunohistochemistry combined with retrograde tracing. Neuroscience 5: 2093–2124, 1980.
 115. Hökfelt, T., and U. Ungerstedt. Specificity of 6‐hydroxy‐dopamine induced degeneration of central monoamine neurones: an electron and fluorescence microscopic study with special reference to intracerebral injection on the nigro‐striatal dopamine system. Brain Res. 60: 269–297, 1973.
 116. Huang, Y. H., and A. Routtenberg. Lateral hypothalamic self‐stimulation pathways in Rattus norvegicus. Physiol. Behav. 7: 419–432, 1971.
 117. Irwin, J., T. N. Tombaugh, R. M. Zacharko, and H. Anisman. Alteration of exploration and the response to food associated cues after treatment with pimozide. Pharmacol. Biochem. Behav. 18: 235–246, 1983.
 118. Iversen, S. D., and G. F. Koob. Behavioral implications of dopaminergic neurons in the mesolimbic system. Adv. Biochem. Psychopharmacol. 16: 209–214, 1977.
 119. Iversen, S. D., S. Wilkinson, and B. Simpson. Enhanced amphetamine responses after frontal cortex lesions in the rat. Eur. J. Pharmacol. 13: 387–390, 1971.
 120. Iwamoto, E. T., and E. L. Way. Circling behaviour and stereotypy induced by intranigral opiate microinjections. J. Pharmacol. Exp. Ther. 203: 347–359, 1977.
 121. Izard, C. E. Patterns of Emotions: A New Analysis of Anxiety and Depression. New York: Academic, 1972.
 122. Janowsky, D., and J. M. Davis. Methylphenidate dextroamphetamine and levoamphetamine. Effects on schizophrenic symptoms. Arch. Gen. Psychiatry 33: 304–308, 1976.
 123. Johanson, C. E. The reinforcing properties of procaine, chloroprocaine and proparacaine in rhesus monkeys. Psychopharmacology 67: 189–194, 1980.
 124. Johansson, O., and T. Hökfelt. Nucleus accumbens: transmitter histochemistry with special reference to peptide‐containing neurons. In: The Neurobiology of the Nucleus Accumbens, edited by R. B. Chronister and J. F. De France. Brunswick, ME: Haer Inst. Electrophysiol. Res., 1981, p. 147–172.
 125. Johnson, R. P., M. Sar, and W. E. Stumpf. A topographic localization of enkephalin on the dopamine neurons of the rat substantia nigra and ventral tegmental area demonstrated by combined histofluorescence‐immunocytochemistry. Brain Res. 194: 566–571, 1980.
 126. Jones, B. E., and R. Y. Moore. Ascending projections of the locus coeruleus in the rat. II. Autoradiographic study. Brain Res. 127: 23–53, 1977.
 127. Jones, D. L., and G. J. Mogenson. Nucleus accumbens to globus pallidus GABA projection: electrophysiological and iontophoretic investigations. Brain Res. 188: 93–105, 1980.
 128. Jones, D. L., and G. J. Mogenson. Nucleus accumbens to globus pallidus GABA projection subserving ambulatory activity. Am. J. Physiol. 238 (Regulatory Integrative Comp. Physiol. 7): R65–R69, 1980.
 129. Jurna, I. Changes in the activity of nigral neurones induced by morphine and other opiates in rats with an intact brain and after prenigral decerebration. Naunyn‐Schmiedeberg's Arch. Pharmacol. 316: 149–154, 1981.
 130. Kanazawa, I., S. Mogaki, O. Muramoto, and S. Kuzuhara. On the origin of substance P‐containing fibres in the entopeduncular nucleus and the substantia nigra of the rat. Brain Res. 184: 481–485, 1980.
 131. Kelley, A. E., L. Stinus, and S. D. Iversen. Interactions between D‐ala‐met‐enkephalin, A10 dopaminergic neurones, and spontaneous behaviour in the rat. Behav. Brain Res. 1: 3–24, 1980.
 132. Kelly, P. H. Unilateral 6‐hydroxydopamine lesions of nigro‐striatal or mesolimbic dopamine‐containing terminals and the drug‐induced rotation of rats. Brain Res. 100: 163–169, 1975.
 133. Kelly, P. H., and S. D. Iversen. Selective 6‐OHDA‐induced destruction of mesolimbic dopamine neurons: abolition of psychostimulant‐induced locomotor activity in rats. Eur. J. Pharmacol. 40: 45–55, 1976.
 134. Kelly, P. H., and K. E. Moore. Mesolimbic dopamine neurons: effects of 6‐hydroxydopamine‐induced destruction and receptor blockade on drug‐induced rotation of rats. Psychopharmacology 55: 35–41, 1977.
 135. Kelly, P. H., P. W. Seviour, and S. D. Iversen. Amphetamine and apomorphine responses in the rat following 6‐OHDA lesions of the nucleus accumbens septi and corpus striatum. Brain Res. 94: 507–522, 1975.
 136. Kobayashi, R. M., M. Brown, and W. Vale. Regional distribution of neurotensin and somatostatin in rat brain. Brain Res. 126: 584–588, 1977.
 137. Koob, G. F., P. J. Fray, and S. D. Iversen. Self‐stimulation at the lateral hypothalamus and locus coeruleus after specific unilateral lesions of the dopamine system. Brain Res. 146: 123–140, 1978.
 138. Koob, G. F., S. J. Riley, S. C. Smith, and T. W. Robbins. Effects of 6‐hydroxydopamine lesions of the nucleus accumbens septi and olfactory tubercle on feeding, locomotor activity, and amphetamine anorexia in the rat. J. Comp. Physiol. Psychol. 92: 917–927, 1978.
 139. Koob, G. F., L. Stinus, and M. Le Moal. Hyperactivity and hypoactivity produced by lesions to the mesolimbic dopamine system. Behav. Brain Res. 3: 341–359, 1981.
 140. Kumar, R. Morphine dependence in rats: secondary reinforcement from environmental stimuli. Psychopharmacologia 25: 332–338, 1972.
 141. Laties, V. G. The modification of drug effects on behavior by external discriminative stimuli. J. Pharmacol. Exp. Ther. 183: 1–13, 1972.
 142. Laties, V. G., and B. Weiss. Influence of drugs on behavior controlled by internal and external stimuli. J. Pharmacol. Exp. Ther. 152: 388–396, 1966.
 143. Lavielle, S., J. P. Tassin, A. M. Thierry, G. Blanc, D. Herve, C. Barthelemy, and J. Glowinski. Blockade by benzodiazepines of the selective high increase in dopamine turnover induced by stress in mesocortical dopaminergic neurons of the rat. Brain Res. 168: 585–594, 1979.
 144. Liebman, J. M., and L. L. Butcher. Effects on self‐stimulation behavior of drugs influencing dopaminergic neurotransmission mechanisms. Naunyn‐Schmiedeberg's Arch. Exp. Pathol. Pharmakol. 277: 305–318, 1973.
 145. Liebman, J. M., and L. L. Butcher. Comparative involvement of dopamine and noradrenaline in rate‐free self‐stimulation in substantia nigra, lateral hypothalamus, and mesencephalic central gray. Naunyn‐Schmiedeberg's Arch. Exp. Pathol. Pharmakol. 284: 167–194, 1974.
 146. Lisoprawski, A., D. Herve, G. Blanc, J. Glowinski, and J. P. Tassin. Selective activation of the mesocortico‐frontal dopaminergic neurons induced by lesion of the habenula in the rat. Brain Res. 183: 229–234, 1980.
 147. Llorens‐Cortes, C., H. Pollard, and J. C. Schwartz. Localization of opiate receptors in substantia nigra evidence by lesion studies. Neurosci. Lett. 12: 165–170, 1979.
 148. Lorens, S. A., and C. L. Mitchell. Influence of morphine on lateral hypothalamic self‐stimulation in the rat. Psycho‐pharmacologia 32: 271–272, 1973.
 149. Lynch, G. S., P. Ballantine II, and B. A. Campbell. Potentiation of behavioral arousal after cortical damage and subsequent recovery. Exp. Neurol. 23: 195–206, 1969.
 150. Lyness, W. H., N. M. Friedle, and K. E. Moore. Destruction of dopaminergic nerve terminals in nucleus accumbens: effect on d‐amphetamine self‐administration. Pharmacol. Biochem. Behav. 11: 553–556, 1979.
 151. Lyon, M., and T. Robbins. The action of central nervous system stimulant drugs: a general theory concerning amphetamine effects. In: Current Developments in Psychopharmacology, edited by W. Essman and L. Valzelli. New York: Spectrum, 1975, p. 89–163.
 152. MacIntosh, N. J. The Psychology of Animal Learning. London: Academic, 1974.
 153. Marshall, J. F. Somatosensory inattention after dopamine‐depleting intracerebral 6‐OHDA injections: spontaneous recovery and pharmacological control. Brain Res. 177: 311–324, 1979.
 154. Marshall, J. F., N. Berrios, and S. Sawyer. Neostriatal dopamine and sensory inattention. J. Comp. Physiol. Psychol. 94: 833–846, 1980.
 155. Marshall, J. F., D. Levitan, and E. M. Stricker. Activation‐induced restoration of sensorimotor function in rats with dopamine‐depleting brain lesions. J. Comp. Physiol. Psychol. 90: 536–546, 1976.
 156. Marshall, J. F., I. S. Richardson, and P. Teitelbaum. Nigrostriatal bundle damage and the lateral hypothalamic syndrome. J. Comp. Physiol. Psychol. 88: 808–830, 1974.
 157. Mason, S. T., R. J. Beninger, H. C. Fibiger, and A. G. Phillips. Pimozide‐induced suppression of responding: evidence against a block of food reward. Pharmacol. Biochem. Behav. 12: 917–923, 1980.
 158. Matthysse, S. Antipsychotic drug actions: a clue to the neuropathology of schizophrenia? Federation Proc. 32: 200–205, 1973.
 159. McGeer, P. L., E. G. McGeer, U. Scherer, and K. Singh. A glutamatergic corticostriatal path? Brain Res. 128: 369–373, 1977.
 160. Mitchell, M. J., N. M. Nicolaou, G. W. Arbuthnott, and C. M. Yates. Increases in dopamine metabolism are not a general feature of intracranial self‐stimulation. Life Sci. 30: 1081–1085, 1982.
 161. Mogenson, G. J. Stability and modification of consummatory behaviors elicited by electrical stimulation of the hypothalamus. Physiol. Behav. 6: 255–260, 1971.
 162. Mogenson, G. J., D. L. Jones, and C. Y. Yim. From motivation to action: functional interface between the limbic system and the motor system. Prog. Neurobiol. 14: 69–97, 1980.
 163. Mogenson, G. J., and A. G. Phillips. Motivation: a psychological construct in search of a physiological substrate. In: Progress in Psychobiology and Physiological Psychology, edited by J. M. Sprague and A. N. Epstein. New York: Academic, 1976, p. 189–243.
 164. Mogenson, G. J., M. Takigawa, A. Robertson, and M. Wu. Self‐stimulation of the nucleus accumbens and ventral tegmental area of Tsai attenuated by microinjections of spiroperidol into the nucleus accumbens. Brain Res. 171: 247–259, 1979.
 165. Mogenson, G. J., M. Wu, and S. K. Manchanda. Locomotor activity initiated by microinfusions of picrotoxin into the ventral tegmental area. Brain Res. 161: 311–319, 1979.
 166. Moore, R. Y., and F. E. Bloom. Central catecholamine neuron systems: anatomy and physiology of the dopamine systems. Annu. Rev. Neurosci. 1: 129–169, 1978.
 167. Moore, R. Y., A. E. Halaris, and B. E. Jones. Serotonin neurons of the midbrain raphe: ascending projections. J. Comp. Neurol. 180: 3, 417–437, 1978.
 168. Mora, F., R. D. Myers, and A. M. Sanguinetti. Self‐stimulation of the MFB or VTA after microinjection of haloperidol into the prefrontal cortex of the rat. Pharmacol. Biochem. Behav. 6: 239–241, 1977.
 169. Mos, J., and C. F. M. van Valkenburg. Specific effect of social stress and aggression on regional dopamine metabolism in rat brain. Neurosci. Lett. 15: 325–327, 1979.
 170. Mucha, R. F., D. van der Kooy, M. O'Shaughnessy, and P. Bucenieks. Drug reinforcement studied by use of place conditioning in rat. Brain Res. 243: 91–105, 1982.
 171. Myers, R. D., and F. Mora. In vivo neurochemical analysis, by push‐pull perfusion, of the mesocortical dopaminergic system of the rat during self‐stimulation. Brain Res. Bull. 2: 105–112, 1977.
 172. Nauta, W. J. H., and V. B. Domesick. Cross roads of limbic and striatal circuitry: hypothalamonigral connections. In: Limbic Mechanisms, edited by K. E. Livingston and O. Hornykiewicz. New York: Plenum, 1978, p. 75–93.
 173. Nauta, W. J. H., G. P. Smith, R. L. M. Faull, and V. B. Domesick. Efferent connections and nigral afferents of the nucleus accumbens septi in the rat. Neuroscience 3: 385–401, 1978.
 174. Newman, R., and S. S. Winans. An experimental study of the ventral striatum of the golden hamster. I. Neuronal connections of the nucleus accumbens. J. Comp. Neurol. 191: 167–192, 1980.
 175. Nowycky, M. C., and R. H. Roth. Dopaminergic neurons: role of presynaptic receptors in the regulation of transmitter biosynthesis. Prog. Neuropsychopharmacol. 2: 139–158, 1978.
 176. Olds, J. Drives and Reinforcements: Behavioral Studies of Hypothalamic Functions. New York: Raven, 1977.
 177. Olds, J., and P. Milner. Positive reinforcement produced by electrical stimulation of septal area and other regions of rat brain. J. Comp. Physiol. Psychol. 47: 419–427, 1954.
 178. Phillips, A. G., S. M. Brooke, and H. C. Fibiger. Effects of amphetamine isomers and neuroleptics on self‐stimulation from the nucleus accumbens and dorsal noradrenergic bundle. Brain Res. 85: 13–32, 1975.
 179. Phillips, A. G., D. A. Carter, and H. C. Fibiger. Differential effects of para‐chlorophenylalanine on self‐stimulation in caudate‐putamen and lateral hypothalamus. Psychopharmacology 49: 23–27, 1976.
 180. Phillips, A. G., D. A. Carter, and H. C. Fibiger. Dopaminergic substrates of intracranial self‐stimulation in the caudate nucleus. Brain Res. 104: 221–232, 1976.
 181. Phillips, A. G., and H. C. Fibiger. Dopaminergic and noradrenergic substrates of positive reinforcement: differential effects of d‐ and I‐ amphetamine. Science 179: 575–577, 1973.
 182. Phillips, A. G., and H. C. Fibiger. Long‐term deficits in stimulation‐induced behaviors and self‐stimulation after 6‐hydroxydopamine administration in rats. Behav. Biol. 16: 127–143, 1976.
 183. Phillips, A. G., and H. C. Fibiger. The role of dopamine in maintaining intracranial self‐stimulation in the ventral tegmentum, nucleus accumbens, and medial prefrontal cortex. Can. J. Physiol. 32: 58–66, 1978.
 184. Phillips, A. G., and H. C. Fibiger. Decreased resistance to extinction after haloperidol: implications for the role of dopamine in reinforcement. Pharmacol. Biochem. Behav. 10: 751–760, 1979.
 185. Phillips, A. G., and F. G. LePiane. Reinforcing effects of morphine microinjection into the ventral tegmental area. Pharmacol. Biochem. Behav. 12: 965–968, 1980.
 186. Phillips, A. G., F. G. LePiane, and H. C. Fibiger. Effects of kainic acid lesions of the striatum on self‐stimulation in the substantia nigra and ventral tegmental area. Behav. Brain Res. 5: 297–310, 1982.
 187. Phillips, A. G., A. C. McDonald, and D. M. Wilkie. Disruption of autoshaped responding to a signal of brain‐stimulation reward by neuroleptic drugs. Pharmacol. Biochem. Behav. 14: 543–548, 1981.
 188. Phillips, A. G., and R. S. Nikaido. Disruption of brain stimulation‐induced feeding by dopamine receptor blockade. Nature London 258: 750–751, 1975.
 189. Phillips, A. G., C. Spyraki, and H. C. Fibiger. Conditioned place preference with amphetamine and opiates as reward stimuli. Attenuation by haloperidol. In: The Neural Basis of Feeding and Reward, edited by B. Hoebel and D. Novin. Brunswick, ME: Haer Inst. Electrophysiol. Res., 1982, p. 455–464.
 190. Phillipson, O. T. Afferent projections to the ventral tegmental area of Tsai and interfascicular nucleus: a horseradish peroxidase study in the rat. J. Comp. Neurol. 187: 117–144, 1979.
 191. Pijnenburg, A. J. J., W. M. M. Honig, and J. M. van Rossum. Inhibition of d‐amphetamine‐induced locomotor activity by injection of haloperidol into the nucleus accumbens of the rat. Psychopharmacologia 41: 87–95, 1975.
 192. Pijnenburg, A. J. J., and J. M. van Rossum. Stimulation of locomotor activity following injection of dopamine into the nucleus accumbens. J. Pharm. Pharmacol. 25: 1003–1005, 1973.
 193. Pollard, H., C. Llorens, J. C. Schwartz, C. Gros, and F. Dray. Localization of opiate receptors and enkephalins in the rat striatum in relationship with the nigro‐striatal dopaminergic system: lesion studies. Brain Res. 151: 392–398, 1978.
 194. Posluns, D. An analysis of chlorpromazine‐induced suppression of the avoidance response. Psychopharmacologia 3: 361–373, 1962.
 195. Price, M. T. C., and H. C. Fibiger. Discriminated escape learning and response to electric shock after 6‐hydroxydopamine lesions of the nigro‐neostriatal dopaminergic projection. Pharmacol. Biochem. Behav. 3: 285–290, 1975.
 196. Pycock, C. J., C. J. Carter, and R. W. Kerwin. Effect of 6‐hydroxydopamine lesions of the medial prefrontal cortex on neurotransmitter systems in subcortical sites in the rat. J. Neurochem. 34: 91–99, 1980.
 197. Pycock, C., and R. Horton. Evidence for an accumbens‐pallidal pathway in the rat and its possible gabaminergic control. Brain Res. 110: 629–634, 1976.
 198. Ranje, C., and U. Ungerstedt. Lack of acquisition in dopamine denervated animals tested in an underwater Y‐maze. Brain Res. 134: 95–111, 1977.
 199. Rapoport, J. L., and M. S. Buchsbaum. Dextroamphetamine: cognitive and behavioral effects in normal prepubertal boys. Science 199: 560–563, 1978.
 200. Reicher, M. A., and E. W. Holman. Location preference and flavour aversion reinforced by amphetamine in rats. Anim. Learn. Behav. 5: 343–346, 1977.
 201. Robbins, T. W. The potentiation of conditioned reinforcement of psychomotor stimulant drugs. A test of Hill's hypothesis. Psychopharmacologia 45: 103–114, 1975.
 202. Robbins, T. W. The acquisition of responding with conditioned reinforcement: effects of pipradrol, methylphenidate, d‐amphetamine and nomifensine. Psychopharmacology 58: 79–87, 1978.
 203. Robbins, T. W., and G. F. Koob. Selective disruption of displacement behaviour by lesions of the mesolimbic dopamine system. Nature London 285: 409–412, 1980.
 204. Robbins, T. W., A. G. Phillips, and B. J. Sahakian. Effects of chlordiazepoxide on tail pinch‐induced eating in rats. Pharmacol. Biochem. Behav. 6: 297–302, 1977.
 205. Roberts, D. C. S., M. E. Corcoran, and H. C. Fibiger. On the role of ascending catecholaminergic systems in intravenous self‐administration of cocaine. Pharmacol. Biochem. Behav. 6: 615–620, 1977.
 206. Roberts, D. C. S., G. F. Koob, P. Klonoff, and H. C. Fibiger. Extinction and recovery of cocaine self‐administration following 6‐hydroxydopamine lesions of the nucleus accumbens. Pharmacol. Biochem. Behav. 12: 781–787, 1980.
 207. Roberts, D. C. S., A. P. Zis, and H. C. Fibiger. Ascending catecholamine pathways and amphetamine‐induced locomotor activity: importance of dopamine and apparent noninvolvement of norepinephrine. Brain Res. 93: 441–454, 1975.
 208. Rolls, E. T., and P. H. Kelly. Neural basis of stimulus‐bound locomotor activity in the rat. J. Comp. Physiol. Psychol. 81: 173–182, 1972.
 209. Ross, S. B. The central stimulatory action of inhibitors of the dopamine uptake. Life Sci. 24: 159–168, 1979.
 210. Rossi, N. A., and L. D. Reid. Affective states associated with morphine injections. Physiol. Psychol. 4: 269–274, 1976.
 211. Routtenberg, A., and C. Malsbury. Brainstem pathways of reward. J. Comp. Physiol. Psychol. 68: 22–30, 1969.
 212. Routtenberg, A., and M. Sloan. Self‐stimulation in the frontal cortex of Rattus norvegicus. Behav. Biol. 7: 567–572, 1972.
 213. Rowland, N., D. M. Marques, and A. E. Fisher. Comparison of the effects of brain dopamine‐depleting lesions upon oral behaviors elicited by tail pinch and electrical brain stimulation. Physiol. Behav. 24: 273–281, 1980.
 214. Sanger, D. J., and D. E. Blackman. Effects of diazepam and ripazepam on two measures of adjunctive drinking in rats. Pharmacol. Biochem. Behav. 5: 139–142, 1976.
 215. Scatton, B. Differential regional development of tolerance to increase in dopamine turnover upon repeated neuroleptic administration. Eur. J. Pharmacol. 46: 363–369, 1977.
 216. Scatton, B. Acute and subacute effects of haloperidol on DOPAC levels in the substantia nigra and ventral tegmental area of the rat brain. Eur. J. Pharmacol. 56: 183–184, 1979.
 217. Scatton, B., S. Bischoff, J. Dedek, and J. Korf. Regional effects of neuroleptics on dopamine metabolism and dopamine‐sensitive adenylate cyclase activity. Eur. J. Pharmacol. 44: 287–292, 1977.
 218. Scatton, B., C. Garret, and L. Julou. Acute and subacute effects of neuroleptics on dopamine synthesis and release in the rat striatum. Naunyn‐Schmiedeberg's Arch. Pharmacol. 289: 419–434, 1975.
 219. Scatton, B., J. Glowinski, and L. Julou. Dopamine metabolism in the mesolimbic and mesocortical dopaminergic systems after single or repeated administrations of neuroleptics. Brain Res. 109: 184–189, 1976.
 220. Schuster, C. R., and T. Thompson. Self‐administration of and behavioral dependence on drugs. Annu. Rev. Pharmacol. 9: 483–502, 1969.
 221. Schuster, C. R., and J. H. Woods. The conditioned reinforcing effects of stimuli associated with morphine reinforcement. Int. J. Addict. 3: 223–230, 1968.
 222. Schwartz, A. S., and P. L. Marchok. Depression of morphine‐seeking behaviour by dopamine inhibition. Nature London 248: 257–258, 1974.
 223. Segal, D. S. Differential effects of para‐chlorophenylalanine on amphetamine‐induced locomotion and stereotypy. Brain Res. 116: 267–276, 1976.
 224. Sherman, J. E., T. Roberts, S. E. Roskam, and E. W. Holman. Temporal properties of rewarding and aversive effects of amphetamine in rats. Pharmacol. Biochem. Behav. 13: 597–599, 1980.
 225. Shore, P. A. Transport and storage of biogenic amines. Annu. Rev. Pharmacol. 12: 209–226, 1972.
 226. Simon, H., B. Scatton, and M. Le Moal. Dopaminergic A10 neurones are involved in cognitive functions. Nature London 286: 150–151, 1980.
 227. Simon, H., L. Stinus, J. P. Tassin, S. Lavielle, G. Blanc, A. M. Thierry, J. Glowinski, and M. Le Moal. Is the dopaminergic mesocorticolimbic system necessary for intracranial self‐stimulation? Biochemical and behavioral studies from A10 cell bodies and terminals. Behav. Neural. Biol. 27: 125–145, 1979.
 228. Skirboll, L. R., A. A. Grace, D. W. Hommer, J. Rehfeld, M. Goldstein, T. Hökfelt, and B. S. Bunney. Peptide‐monoamine coexistence: studies of the actions of cholecystokinin‐like peptide on the electrical activity of midbrain dopamine neurons. Neuroscience 6: 2111–2124, 1981.
 229. Smith, S. G., and W. M. Davis. Behavioral control by stimuli associated with acquisition of morphine self‐administration. Behav. Biol. 9: 777–780, 1973.
 230. Snyder, S. H. Amphetamine psychosis: a model schizophrenia mediated by catecholamines. Am. J. Psychiatry 130: 61–67, 1973.
 231. Somogyi, P., J. P. Bolam, S. Totterdell, and A. D. Smith. Monosynaptic input from the nucleus accumbens‐ventral striatum region to retrogradely labelled nigrostriatal neurones. Brain Res. 217: 245–263, 1981.
 232. Soper, W. Y., and R. A. Wise. Hypothalamically induced eating: eating from ‘non‐eaters’ with diazepam. Life Sci. 1: 79–84, 1971.
 233. Spyraki, C., and H. C. Fibiger. Behavioural evidence for supersensitivity of postsynaptic dopamine receptors in the mesolimbic system after chronic administration of desipramine. Eur. J. Pharmacol. 74: 195–206, 1981.
 234. Spyraki, C., H. C. Fibiger, and A. G. Phillips. Attenuation by haloperidol of place preference conditioning using food reinforcement. Psychopharmacology 77: 379–382, 1982.
 235. Spyraki, C., H. C. Fibiger, and A. G. Phillips. Dopaminergic substrates of amphetamine‐induced place preference conditioning. Brain Res. 253: 185–193, 1982.
 236. Spyraki, C., H. C. Fibiger, and A. G. Phillips. Cocaine‐induced place preference conditioning: lack of effects of neuroleptics and 6‐hydroxydopamine lesions. Brain Res. 253: 195–203, 1982.
 237. Spyraki, C., H. C. Fibiger, and A. G. Phillips. Attenuation of heroin reward in rats by disruption of the mesolimbic dopamine system. Psychopharmacology 79: 278–283, 1983.
 238. Staines, W. A., J. I. Nagy, S. R. Vincent, and H. C. Fibiger. Neurotransmitters contained in the efferents of the striatum. Brain Res. 194: 391–402, 1980.
 239. Stein, L. Self‐stimulation of the brain and the central stimulant action of amphetamine. Federation Proc. 23: 836–841, 1964.
 240. Stein, L. Reward transmitters: catecholamines and opioids. In: Psychopharmacology: A Generation of Progress, edited by M. A. Lipton, A. Di Mascio, and K. F. Killam. New York: Raven, 1978, p. 569–581.
 241. Stevens, J. R. An anatomy of schizophrenia? Arch. Gen. Psychiatry 29: 177–189, 1973.
 242. Stinus, L., A. M. Thierry, G. Blanc, J. Glowinski, and B. Cardo. Self‐stimulation and catecholamines. III. Effect of imposed or self‐stimulation in the area ventralis tegmenti on catecholamine utilization in the rat brain. Brain Res. 64: 199–210, 1973.
 243. Swanson, L. W., and W. M. Cowan. A note on the connections and development of the nucleus accumbens. Brain Res. 92: 324–330, 1975.
 244. Sykes, D. H., V. I. Douglas, G. Weiss, and K. K. Minde. Attention in hyperactive children and the effect of methyl‐phenidate (Ritalin). J. Child Psychol. Psychiatry Allied Discip. 12: 129–139, 1971.
 245. Szostak, C., and T. N. Tombaugh. Use of fixed consecutive number schedule of reinforcement to investigate the effects of pimozide on behavior controlled by internal and external stimuli. Pharmacol. Biochem. Behav. 15: 609–617, 1981.
 246. Tassin, J. P., A. Cheramy, G. Blanc, A. M. Thierry, and J. Glowinski. Topographical distribution of dopaminergic innervation and of dopaminergic receptors in the rat striatum. I. Microestimation of [3H]dopaminergic uptake and dopamine content in microdiscs. Brain Res. 107: 291–301, 1976.
 247. Tatum, A. L., M. H. Seevers, and K. H. Collins. Morphine addiction and its physiological interpretation based on experimental evidences. J. Pharmacol. Exp. Ther. 36: 447–475, 1927.
 248. Thierry, A. M., J. P. Tassin, G. Blanc, and J. Glowinski. Selective activation of the mesocortical DA system by stress. Nature London 263: 242–244, 1976.
 249. Thompson, D. M. Stimulus control and drug effects. In: Contemporary Research in Behavioral Pharmacology, edited by D. E. Blackman and D. J. Sanger. New York: Plenum, 1978, p. 159–208.
 250. Thornburg, J. E., and K. E. Moore. Dopamine and norepinephrine uptake by rat brain synaptosomes: relative inhibitory potencies of I‐ and d‐amphetamine and amantadine. Res. Commun. Chem. Pathol. Pharmacol. 5: 81–89, 1973.
 251. Thurston, C. M., M. P. Sobol, J. Swanson, and M. Kinsbourne. Effects of methylphenidate (Ritalin) on selective attention in hyperactive children. J. Abnorm. Child Psychol. 7: 471–481, 1979.
 252. Tombaugh, T. N. Effects of pimozide on nondiscriminated and discriminated performance in the pigeon. Psychopharmacology 73: 137–141, 1981.
 253. Tombaugh, T. N., H. Anisman, and J. Tombaugh. Extinction and dopamine receptor blockade after intermittent reinforcement training: failure to observe functional equivalence. Psychopharmacology 70: 19–28, 1980.
 254. Tombaugh, T. N., L. J. Grandmaison, and K. A. Zito. Establishment of secondary reinforcement in sign tracking and place preference tests following pimozide treatment. Pharmacol. Biochem. Behav. 17: 665–670, 1982.
 255. Tombaugh, T. N., M. A. Ritch, and D. T. Shepherd. Effects of pimozide on accuracy of performance and distribution of correct responding on a simultaneous discrimination task in the rat. Pharmacol. Biochem. Behav. 13: 859–862, 1980.
 256. Tombaugh, T. N., C. Szostak, P. Voorneveld, and J. W. Tombaugh. Failure to obtain functional equivalence between dopamine receptor blockade and extinction: evidence supporting a sensory‐motor conditioning hypothesis. Pharmacol. Biochem. Behav. 16: 67–72, 1982.
 257. Tomkins, S. S. Affect, Imagery, Consciousness. The Positive Affects. New York: Springer, 1962, vol. 1.
 258. Uhl, G. R., R. R. Goodman, M. J. Kuhar, S. R. Childers, and S. H. Snyder. Immunohistochemical mapping of enkephalin containing cell bodies, fibers and nerve terminals in the brain stem of the rat. Brain Res. 166: 75–94, 1979.
 259. Ungerstedt, U. Stereotaxic mapping of the monamine pathways in the rat brain. Acta Physiol. Scand. Suppl. 367: 1–48, 1971.
 260. Ungerstedt, U., and G. W. Arbuthnott. Quantitative recording of rotational behavior in rats after 6‐hydroxydopamine lesions of the nigrostriatal dopamine system. Brain Res. 24: 485–493, 1970.
 261. Valenstein, E. S. Behavior elicited by hypothalamic stimulation. Brain Behav. Evol. 2: 295–316, 1969.
 262. Valenstein, E. S., V. C. Cox, and J. W. Kakolewski. Modification of motivated behavior elicited by electrical stimulation of the hypothalamus. Science 159: 1119–1121, 1968.
 263. Valenstein, E. S., V. C. Cox, and J. W. Kakolewski. Reexamination of the role of the hypothalamus in motivation. Psychol. Rev. 77: 16–31, 1970.
 264. Van der Kooy, D., R. F. Mucha, M. O'Shaughnessy, and P. Buckenieks. Reinforcing effects of brain microinjections of morphine revealed by conditioned place preference. Brain Res. 243: 107–117, 1982.
 265. Veening, J. G., F. M. Cornelissen, and P. A. J. M. Lieven. The topical organization of the afferents to the caudatoputa‐men of the rat. A horseradish peroxidase study. Neuroscience 5: 1253–1268, 1980.
 266. Von Voigtlander, P. F., and K. E. Moore. Turning behavior of mice with unilateral 6‐hydroxydopamine lesions in the striatum: effects of apomorphine, L‐DOPA, amanthadine, amphetamine and other psychomotor stimulants. Neuropharmacology 12: 451–462, 1973.
 267. Walaas, I., and F. Fonnum. The effects of surgical and chemical lesions on neurotransmitter candidates in the nucleus accumbens of the rat. Neuroscience 4: 209–216, 1979.
 268. Walaas, I., and F. Fonnum. Biochemical evidence for γ‐aminobutyrate containing fibres from the nucleus accumbens to the substantia nigra and ventral tegmental area in the rat. Neuroscience 5: 63–72, 1980.
 269. Wang, R. Y. Dopaminergic neurons in the rat ventral tegmental area. I. Identification and characterization. Brain Res. Rev. 3: 123–140, 1981.
 270. Wang, R. Y. Dopaminergic neurons in the rat ventral tegmental area. II. Evidence for autoregulation. Brain Res. Rev. 3: 141–151, 1981.
 271. Wang, R. Y. Dopaminergic neurons in the rat ventral tegmental area. III. Effects of d‐ and I‐amphetamine. Brain Res. Rev. 3: 153–165, 1981.
 272. Wauquier, A. The influence of psychoactive drugs on brain self‐stimulation in rats: a review. In: Brain Stimulation Reward, edited by A. Wauquier and E. T. Rolls. New York: Elsevier, 1976, p. 123–170.
 273. Weeks, J. R. Experimental morphine addiction: method for automatic intravenous injections in unrestrained rats. Science 138: 143–144, 1962.
 274. Westerink, B. H. C., B. Lejeune, J. Korf, and H. M. van Praag. On the significance of regional dopamine metabolism in the rat brain for the classification of centrally acting drugs. Eur. J. Pharmacol. 42: 179–190, 1977.
 275. White, N., Z. Brown, and M. Yachnin. Effects of catecholamine manipulations on three different self‐stimulation behaviors. Pharmacol. Biochem. Behav. 9: 273–278, 1978.
 276. Wise, R. A. Catecholamine theories of reward: a critical review. Brain Res. 152: 215–247, 1978.
 277. Wise, R. A., J. Spindler, H. De Wit, and G. J. Gerber. Neuroleptic‐induced “anhedonia” in rats: pimozide blocks the reward quality of food. Science 201: 262–264, 1978.
 278. Wolf, P., H. R. Olpe, D. Avrith, and H. L. Haas. GABAergic inhibition of neurons in the ventral tegmental area. Experientia 34: 73–74, 1978.
 279. Woodruff, G., and D. R. Williams. The associative relation underlying autoshaping in the pigeon. J. Exp. Anal. Behav. 26: 1–13, 1976.
 280. Woolverton, W. L., and R. L. Balster. Effects of antipsychotic compounds in rhesus monkeys given a choice between cocaine and food. Drug Alcohol Depend. 8: 69–78, 1981.
 281. Yim, C. Y., and G. J. Mogenson. Effect of picrotoxin and nipecotic acid on inhibitory response of dopaminergic neurons in the ventral tegmental area to stimulation of the nucleus accumbens. Brain Res. 199: 466–472, 1980.
 282. Yim, C. Y., and G. J. Mogenson. Electrophysiological studies of neurons in the ventral tegmental area of Tsai. Brain Res. 181: 301–313, 1980.
 283. Yokel, R. A., and R. A. Wise. Attenuation of intravenous amphetamine reinforcement by central dopamine blockade in rats. Psychopharmacology 48: 311–318, 1976.
 284. Zarevics, P., and P. E. Setler. Simultaneous rate‐independent and rate‐dependent assessment of intracranial self‐stimulation: evidence for the direct involvement of dopamine in brain reinforcement mechanisms. Brain Res. 169: 499–512, 1979.

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H. C. Fibiger, A. G. Phillips. Reward, Motivation, Cognition: Psychobiology of Mesotelencephalic Dopamine Systems. Compr Physiol 2011, Supplement 4: Handbook of Physiology, The Nervous System, Intrinsic Regulatory Systems of the Brain: 647-675. First published in print 1986. doi: 10.1002/cphy.cp010412