The authors review the evidence that cocaine exerts its rewarding effects through the acute activation of dopamine (DA) pathways in the brain. Chronic cocaine administration is hypothesized to lead to DA depletion, which results in cocaine craving and cocaine abstinence states. Treatment of these states with bromocriptine, a DA antagonist, appears to have efficacy with acute and maintenance trials, and may represent a new adjunctive treatment for cocaine abuse. DA antagonists appear to exacerbate cocaine craving, which is consistent with the DA depletion hypothesis of chronic cocaine abuse. Theoretical issues relating to drug addiction and endogenous reward centers are discussed.
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References
1.
WetliC. V. and WrightR. K.Death Caused by Recreational Cocaine Use, Journal of the American Medical Association, 241, pp. 2519–2522, 1979.
2.
LichtenfeldP. J.RubinD. B., and FeldmanR. S.Subarachnoid Hemorrhage Precipitated by Cocaine Snorting, Archives of Neurology, 41, pp. 223–224, 1984.
3.
GayG. R.Clinical Management of Acute and Chronic Cocaine Poisoning, Annals of Emergency Medicine, 11, pp. 562–570, 1982.
4.
GoldM. S. and DackisC. A.New Insights and Treatments: Opiate Withdrawal and Cocaine Addiction, Clinical Therapeutics, 7: 1, pp. 6–21, 1984.
5.
PostR. M.Cocaine Psychosis: A Continuum Model, American Journal of Psychiatry, 132, pp. 225–231, 1975.
6.
SeigelR. K.Cocaine Hallucinations, American Journal of Psychiatry, 135, pp. 309–314, 1978.
7.
OldsJ. and MilnerP. M.Positive Reinforcement Produced by Electrical Stimulation of the Septal Area and Other Regions of Rat Brain, Journal of Comprehensive Physiology and Psychology, 47, pp. 419–427, 1954.
8.
OldsJ.Pleasure Centers in the Brain, Scientific American, 195, pp. 105–116, 1956.
9.
WiseR. A.Catecholamine Theories of Reward: A Critical Review, Brain Research, 152, pp. 215–247, 1978.
10.
DavisW. M. and SmithS. G.Blocking Effect of Alpha-Methyltyrosine on Amphetamine-based Reinforcement, Journal of Pharmacy and Pharmacology, 25, pp. 174–177, 1973.
11.
SteinL., Chemistry of Purposive Behavior, in Reinforcement and Behavior, TappJ. T. (ed.), Academic Press, New York, pp. 328–355, 1969.
12.
WilsonM. C. and SchusterC. R.The Effects of Chlorpromazine on Psychomotor Stimulant Self-administration in the Rhesus Monkey, Psychopharmacologia, 26, pp. 115–126, 1972.
13.
deWittH. and WiseR. A.A Blockade of Cocaine Reinforcement in Rats with the Dopamine Receptor Blocker Pimozide But Not with the Noradrenergic Blockers Phentolamine or Phenoxybenzamine, Canadian Journal of Psychology, 31, pp. 195–203, 1977.
14.
RisnerM. E. and JonesB. E.Intravenous Self-administration of Cocaine and Norcocaine by Dogs, Psychopharmacology, 71, pp. 83–89, 1980.
15.
DavisW. M. and SmithS. G.Effect of Haloperidol on (+)-amphetamine Self-administration, Journal of Pharmacy and Pharmacology, 27, pp. 540–542, 1975.
16.
YokelR. A. and WiseR. A.Increased Lever Pressing for Amphetamine After Pimozide in Rats: Implications for a Dopamine Theory of Reward, Science, 187, pp. 547–549, 1975.
17.
YokelR. A. and WiseR. A.Attenuation of Intravenous Amphetamine Reinforcement by Central Dopamine Blockade in Rats, Psychopharmacology, 48, pp. 311–318, 1976.
18.
RisnerM. E. and JonesB. E.Role of Noradrenergic and Dopaminergic Processes in Amphetamine Self-administration, Pharmacologic and Biochemical Behavior, 5, pp. 477–482, 1976.
19.
GunneL. M.AnggardE., and JonssonL. E.Clinical Trials with Amphetamine-blocking Drugs, Psychiar Neurol Neurochir, 75, pp. 225–226, 1972.
20.
AngristB.LeeH. K., and GershonS.The Antagonism of Amphetamine Induced Symptomatology by a Neuroleptic, American Journal of Psychiatry, 131, p. 817, 1974.
21.
YokelR. A. and WiseR. A.Amphetamine-type Reinforcement by Dopamine Agonists in the Rat, Psychopharmacology, 58, pp. 289–296, 1978.
22.
BaxterB. L.GluckmanM. I.SteinL., Self-injection of Apomorphine in the Rat: Positive Reinforcement by a Dopamine Receptor Stimulant, Pharmacologic and Biochemical Behavior, 2, pp. 387–391, 1975.
23.
DavisW. M. and SmithS. G.Catecholaminergic Mechanisms of Reinforcement: Direct Assessment by Drug Self-stimulation, Life Sciences, 20, pp. 483–492, 1977.
24.
RobertsD. C. S. and KoobG.Disruption of Cocaine Self-administration Following 6-hydroxydopamine Lesions of the Vental Segmental Area in Rats, Pharmacologic and Biochemical Behavior, 17, pp. 901–904, 1982.
25.
RobertsD. H. C.CorcoranM. E., and FibigerH. C., On the Role of Ascending Catecholamine Systems in Intravenous Self-administration of Cocaine, Pharmacologic and Biochemical Behavior, 6, pp. 615–620, 1977.
26.
GoedersN. E. and SmithJ. E.Cortical Dopaminergic Involvement in Cocaine Reinforcement, Science, 221, pp. 773–775, 1983.
27.
RossS. B. and RenyiA. L.Uptake of Some Tritiated Sympathomimetic Amines by Mouse Brain Cortex in Vitro, Acta Pharmacology and Toxicology, 24, pp. 297–309, 1966.
28.
DigiulioA. M.GroppettiA.CattabeniF., Significance of Dopamine Metabolites in the Evaluation of Drugs Acting on Dopaminergic Neurons, European Journal of Pharmacology, 52, pp. 201–207, 1978.
29.
CreeseI.BurtD. R., and SnyderS. H.Dopamine Receptor Binding Enhancement Accompanies Lesion-induced Behavioral Supersensitivity, Science, 197, pp. 596–598, 1977.
30.
RaffM.Self-regulation of Membrane Receptors, Nature, 259, pp. 265–266, 1976.
31.
BorisonR. L.HitriA.KlawansH. L., A New Animal Model for Schizophrenia: Behavioral and Receptor Binding Studies, in Catecholamines: Basic and Clinical Frontiers, UsdinE.KopinI. J. and BarchiasJ. (eds.), Pergamon Press, New York, pp. 719–721, 1979.
32.
TaylorD. and HoB. T.Comparison of Inhibition on Monoamine Uptake by Cocaine, Methylphenidate and Amphetamine, Research in Community Chemical Pathology and Pharmacology, 21, pp. 67–75, 1978.
33.
MemoM.PradhanS., and HanbauerI.Cocaine-induced Supersensitivity of Striatal Dopamine Receptors: Role of Endogenous Calmodulin, Neuropharmacology, 20, pp. 1145–1150, 1981.
34.
PradhanS.RoyS. N., and PradhanS. N.Correlation of Behavioral and Neurochemical Effects of Acute Administration of Cocaine in Rats, Life Sciences, 22, pp. 265–266, 1976.
35.
TaylorD. and HoB. T.Neurochemical Effects of Cocaine Following Acute and Repeated Injection, Journal of Neuroscience Research, 3, pp. 95–101, 1977.
36.
CarlssonA.HillarpN. A., and WaldeckB.Analysis of the Mg++-ATP Dependent Storage Mechanism in the Amine Granule of the Adrenal Medulla, Acta Psychology Scandinavian Supplement, 215: 6, pp. 1–38, 1963.
37.
PatrickR. L., and BarchasJ. D.Potentiation by Cocaine of the Stimulus-induced Increase in Dopamine Synthesis in Rat Brain Striatal Synaptosomes, Neuropharmacology, 16: 5, p. 327, 1977.
38.
DackisC. A.GoldM. S.EstroffT. W., Hyperprolactinemia in Cocaine Abuse, Society for the Neuroscience Abstract, 10, p. 1099, 1984.
39.
DackisC. A. and GoldM. S.Bromocriptine as a Treatment of Cocaine Abuse, Lancet, 8438, pp. 1151–1152.
