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. 1994 Mar;61(2):213–221. doi: 10.1901/jeab.1994.61-213

Effects of mesolimbic dopamine depletion on responding maintained by cocaine and food.

S B Caine 1, G F Koob 1
PMCID: PMC1334409  PMID: 8169570

Abstract

The hypothesis that mesolimbic dopamine is selectively involved in cocaine reinforcement was investigated in the rat. Animals were trained under a multiple schedule in which responding was reinforced by intravenous cocaine (0.75 mg/kg/injection) or food (45-mg pellets) under fixed-ratio 15 schedule requirements in alternate 30-min components of a 2-hr daily session. Infusion of the catecholaminergic neurotoxin 6-hydroxydopamine, but not the vehicle solution, into the region of the nucleus accumbens and olfactory tubercle produced selective reductions in cocaine self-administration without significantly altering responding maintained by food within the same sessions. This effect was reproduced in intact animals by substituting saline for cocaine in the self-administration component. These results support the hypothesis that the reinforcing effects of cocaine are dependent upon mesolimbic dopamine and demonstrate that cocaine self-administration can be disrupted in animals without altering behavior maintained by a nondrug reinforcer.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Amalric M., Koob G. F. Depletion of dopamine in the caudate nucleus but not in nucleus accumbens impairs reaction-time performance in rats. J Neurosci. 1987 Jul;7(7):2129–2134. doi: 10.1523/JNEUROSCI.07-07-02129.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beninger R. J., Cheng M., Hahn B. L., Hoffman D. C., Mazurski E. J., Morency M. A., Ramm P., Stewart R. J. Effects of extinction, pimozide, SCH 23390, and metoclopramide on food-rewarded operant responding of rats. Psychopharmacology (Berl) 1987;92(3):343–349. doi: 10.1007/BF00210842. [DOI] [PubMed] [Google Scholar]
  3. Ettenberg A., Camp C. H. A partial reinforcement extinction effect in water-reinforced rats intermittently treated with haloperidol. Pharmacol Biochem Behav. 1986 Dec;25(6):1231–1235. doi: 10.1016/0091-3057(86)90117-6. [DOI] [PubMed] [Google Scholar]
  4. Ettenberg A. Dopamine, neuroleptics and reinforced behavior. Neurosci Biobehav Rev. 1989 Summer-Fall;13(2-3):105–111. doi: 10.1016/s0149-7634(89)80018-1. [DOI] [PubMed] [Google Scholar]
  5. Felice L. J., Felice J. D., Kissinger P. T. Determination of catecholamines in rat brain parts by reverse-phase ion-pair liquid chromatography. J Neurochem. 1978 Dec;31(6):1461–1465. doi: 10.1111/j.1471-4159.1978.tb06573.x. [DOI] [PubMed] [Google Scholar]
  6. Fibiger H. C., Phillips A. G., Zis A. P. Deficits in instrumental responding after 6-hydroxydopamine lesions of the nigro-neostriatal dopaminergic projection. Pharmacol Biochem Behav. 1974 Jan-Feb;2(1):87–96. doi: 10.1016/0091-3057(74)90139-7. [DOI] [PubMed] [Google Scholar]
  7. Gold L. H., Swerdlow N. R., Koob G. F. The role of mesolimbic dopamine in conditioned locomotion produced by amphetamine. Behav Neurosci. 1988 Aug;102(4):544–552. doi: 10.1037//0735-7044.102.4.544. [DOI] [PubMed] [Google Scholar]
  8. Griffiths R. R., Wurster R. M., Brady J. V. Discrete-trial choice procedure: effects of naloxone and methadone on choice between food and heroin. Pharmacol Rev. 1975 Sep;27(3):357–365. [PubMed] [Google Scholar]
  9. Hernandez L., Hoebel B. G. Feeding and hypothalamic stimulation increase dopamine turnover in the accumbens. Physiol Behav. 1988;44(4-5):599–606. doi: 10.1016/0031-9384(88)90324-1. [DOI] [PubMed] [Google Scholar]
  10. Horvitz J. C., Ettenberg A. Haloperidol blocks the response-reinstating effects of food reward: a methodology for separating neuroleptic effects on reinforcement and motor processes. Pharmacol Biochem Behav. 1988 Dec;31(4):861–865. doi: 10.1016/0091-3057(88)90396-6. [DOI] [PubMed] [Google Scholar]
  11. Kelley A. E., Stinus L. Disappearance of hoarding behavior after 6-hydroxydopamine lesions of the mesolimbic dopamine neurons and its reinstatement with L-dopa. Behav Neurosci. 1985 Jun;99(3):531–545. doi: 10.1037//0735-7044.99.3.531. [DOI] [PubMed] [Google Scholar]
  12. Koob G. F., Riley S. J., Smith S. C., Robbins T. W. 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. 1978 Oct;92(5):917–927. doi: 10.1037/h0077542. [DOI] [PubMed] [Google Scholar]
  13. Kornetsky C., Huston-Lyons D., Porrino L. J. The role of the olfactory tubercle in the effects of cocaine, morphine and brain-stimulation reward. Brain Res. 1991 Feb 8;541(1):75–81. doi: 10.1016/0006-8993(91)91076-d. [DOI] [PubMed] [Google Scholar]
  14. Le Moal M., Stinus L., Simon H., Tassin J. P., Thierry A. M., Blanc G., Glowinski J., Cardo B. Behavioral effects of a lesion in the ventral mesencephalic tegmentum: evidence for involvement of A10 dopaminergic neurons. Adv Biochem Psychopharmacol. 1977;16:237–245. [PubMed] [Google Scholar]
  15. Marshall J. F., Richardson J. S., Teitelbaum P. Nigrostriatal bundle damage and the lateral hypothalamic syndrome. J Comp Physiol Psychol. 1974 Nov;87(5):808–830. doi: 10.1037/h0037223. [DOI] [PubMed] [Google Scholar]
  16. Miller R., Wickens J. R., Beninger R. J. Dopamine D-1 and D-2 receptors in relation to reward and performance: a case for the D-1 receptor as a primary site of therapeutic action of neuroleptic drugs. Prog Neurobiol. 1990;34(2):143–183. doi: 10.1016/0301-0082(90)90005-2. [DOI] [PubMed] [Google Scholar]
  17. Nakajima S., Baker J. D. Effects of D2 dopamine receptor blockade with raclopride on intracranial self-stimulation and food-reinforced operant behaviour. Psychopharmacology (Berl) 1989;98(3):330–333. doi: 10.1007/BF00451683. [DOI] [PubMed] [Google Scholar]
  18. Pettit H. O., Ettenberg A., Bloom F. E., Koob G. F. Destruction of dopamine in the nucleus accumbens selectively attenuates cocaine but not heroin self-administration in rats. Psychopharmacology (Berl) 1984;84(2):167–173. doi: 10.1007/BF00427441. [DOI] [PubMed] [Google Scholar]
  19. Robbins T. W., Everitt B. J. Comparative functions of the central noradrenergic, dopaminergic and cholinergic systems. Neuropharmacology. 1987 Jul;26(7B):893–901. doi: 10.1016/0028-3908(87)90067-0. [DOI] [PubMed] [Google Scholar]
  20. Robbins T. W., Koob G. F. Selective disruption of displacement behaviour by lesions of the mesolimbic dopamine system. Nature. 1980 Jun 5;285(5764):409–412. doi: 10.1038/285409a0. [DOI] [PubMed] [Google Scholar]
  21. Robbins T. W., Roberts D. C., Koob G. F. Effects of d-amphetamine and apomorphine upon operant behavior and schedule-induced licking in rats with 6-hydroxydopamine-induced lesions of the nucleus accumbens. J Pharmacol Exp Ther. 1983 Mar;224(3):662–673. [PubMed] [Google Scholar]
  22. Roberts D. C., Corcoran M. E., Fibiger H. C. On the role of ascending catecholaminergic systems in intravenous self-administration of cocaine. Pharmacol Biochem Behav. 1977 Jun;6(6):615–620. doi: 10.1016/0091-3057(77)90084-3. [DOI] [PubMed] [Google Scholar]
  23. Roberts D. C., Koob G. F., Klonoff P., Fibiger H. C. Extinction and recovery of cocaine self-administration following 6-hydroxydopamine lesions of the nucleus accumbens. Pharmacol Biochem Behav. 1980 May;12(5):781–787. doi: 10.1016/0091-3057(80)90166-5. [DOI] [PubMed] [Google Scholar]
  24. Rolls E. T., Rolls B. J., Kelly P. H., Shaw S. G., Wood R. J., Dale R. The relative attenuation of self-stimulation, eating and drinking produced by dopamine-receptor blockade. Psychopharmacologia. 1974;38(3):219–230. doi: 10.1007/BF00421374. [DOI] [PubMed] [Google Scholar]
  25. Taghzouti K., Simon H., Louilot A., Herman J. P., Le Moal M. Behavioral study after local injection of 6-hydroxydopamine into the nucleus accumbens in the rat. Brain Res. 1985 Sep 30;344(1):9–20. doi: 10.1016/0006-8993(85)91184-9. [DOI] [PubMed] [Google Scholar]
  26. Taylor J. R., Robbins T. W. Enhanced behavioural control by conditioned reinforcers following microinjections of d-amphetamine into the nucleus accumbens. Psychopharmacology (Berl) 1984;84(3):405–412. doi: 10.1007/BF00555222. [DOI] [PubMed] [Google Scholar]
  27. Tombaugh T. N., Tombaugh J., Anisman H. Effects of dopamine receptor blockade on alimentary behaviors: home cage food consumption, magazine training, operant acquisition, and performance. Psychopharmacology (Berl) 1979;66(3):219–225. doi: 10.1007/BF00428309. [DOI] [PubMed] [Google Scholar]
  28. Ungerstedt U. Adipsia and aphagia after 6-hydroxydopamine induced degeneration of the nigro-striatal dopamine system. Acta Physiol Scand Suppl. 1971;367:95–122. doi: 10.1111/j.1365-201x.1971.tb11001.x. [DOI] [PubMed] [Google Scholar]
  29. Willner P., Phillips G., Sampson D., Muscat R. Time-dependent and schedule-dependent effects of dopamine receptor blockade. Behav Pharmacol. 1989;1(2):169–176. [PubMed] [Google Scholar]
  30. Wise R. A., Schwartz H. V. Pimozide attenuates acquisition of lever-pressing for food in rats. Pharmacol Biochem Behav. 1981 Oct;15(4):655–656. doi: 10.1016/0091-3057(81)90225-2. [DOI] [PubMed] [Google Scholar]
  31. Wise R. A., Spindler J., deWit H., Gerberg G. J. Neuroleptic-induced "anhedonia" in rats: pimozide blocks reward quality of food. Science. 1978 Jul 21;201(4352):262–264. doi: 10.1126/science.566469. [DOI] [PubMed] [Google Scholar]

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