Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1990 Apr;99(4):736–740. doi: 10.1111/j.1476-5381.1990.tb12999.x

Actions of cocaine on rat nucleus accumbens neurones in vitro.

N Uchimura 1, R A North 1
PMCID: PMC1917561  PMID: 2193689

Abstract

1. Intracellular recordings were made from 103 neurones of the rat nucleus accumbens in vitro. 2. Dopamine (3-100 microM; in sulpiride, 1 microM) hyperpolarized neurones (79%) by acting at D1 receptors: dopamine (3-100 microM; in SCH23390, 1 microM) depolarized neurones (55%) by acting at D2 receptors. 5-Hydroxytryptamine (1-100 microM) depolarized 86% neurones. 3. Both actions of dopamine as well as the effect of 5-hydroxytryptamine were potentiated by cocaine (0.3-30 microM), which had no effect of its own on membrane potential. 4. Dose-ratio was computed as [(concentration of agonist causing a 4 mV potential change in cocaine)/(concentration of agonist causing a 4 mV potential change without cocaine)]. Cocaine (1-30 microM) caused the same dose-ratio whether dopamine depolarizations (D2) or hyperpolarizations (D1) were measured; the dose-ratio ranged from 2 (1 microM) to 50 (30 microM). 5. Responses to 5-hydroxytryptamine were increased more than responses to dopamine; cocaine 1 microM gave a dose-ratio of 13.4 and at 30 microM gave a dose-ratio of 118. 6. It is concluded that cocaine acts to inhibit the uptake of dopamine and 5-hydroxytryptamine in slices of rat nucleus accumbens; lower concentrations of cocaine (0.3 to 1 microM) are particularly effective in potentiating the action of 5-hydroxytryptamine.

Full text

PDF
740

Selected References

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

  1. Higashi H., Inanaga K., Nishi S., Uchimura N. Enhancement of dopamine actions on rat nucleus accumbens neurones in vitro after methamphetamine pre-treatment. J Physiol. 1989 Jan;408:587–603. doi: 10.1113/jphysiol.1989.sp017478. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Kelly P. H., Roberts D. C. Effects of amphetamine and apomorphine on locomotor activity after 6-OHDA and electrolytic lesions of the nucleus accumbens septi. Pharmacol Biochem Behav. 1983 Jul;19(1):137–143. doi: 10.1016/0091-3057(83)90322-2. [DOI] [PubMed] [Google Scholar]
  3. Koob G. F., Bloom F. E. Cellular and molecular mechanisms of drug dependence. Science. 1988 Nov 4;242(4879):715–723. doi: 10.1126/science.2903550. [DOI] [PubMed] [Google Scholar]
  4. Lacey M. G., Mercuri N. B., North R. A. Actions of cocaine on rat dopaminergic neurones in vitro. Br J Pharmacol. 1990 Apr;99(4):731–735. doi: 10.1111/j.1476-5381.1990.tb12998.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Nicolaysen L. C., Pan H. T., Justice J. B., Jr Extracellular cocaine and dopamine concentrations are linearly related in rat striatum. Brain Res. 1988 Jul 26;456(2):317–323. doi: 10.1016/0006-8993(88)90234-x. [DOI] [PubMed] [Google Scholar]
  6. North R. A., Uchimura N. 5-Hydroxytryptamine acts at 5-HT2 receptors to decrease potassium conductance in rat nucleus accumbens neurones. J Physiol. 1989 Oct;417:1–12. doi: 10.1113/jphysiol.1989.sp017786. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Pijnenburg A. J., Honig W. M., Van der Heyden J. A., Van Rossum J. M. Effects of chemical stimulation of the mesolimbic dopamine system upon locomotor activity. Eur J Pharmacol. 1976 Jan;35(1):45–58. doi: 10.1016/0014-2999(76)90299-5. [DOI] [PubMed] [Google Scholar]
  8. Ritz M. C., Lamb R. J., Goldberg S. R., Kuhar M. J. Cocaine receptors on dopamine transporters are related to self-administration of cocaine. Science. 1987 Sep 4;237(4819):1219–1223. doi: 10.1126/science.2820058. [DOI] [PubMed] [Google Scholar]
  9. Snyder S. H., Coyle J. T. Regional differences in H3-norepinephrine and H3-dopamine uptake into rat brain homogenates. J Pharmacol Exp Ther. 1969 Jan;165(1):78–86. [PubMed] [Google Scholar]
  10. Steinbusch H. W. Distribution of serotonin-immunoreactivity in the central nervous system of the rat-cell bodies and terminals. Neuroscience. 1981;6(4):557–618. doi: 10.1016/0306-4522(81)90146-9. [DOI] [PubMed] [Google Scholar]
  11. Surprenant A., Williams J. T. Inhibitory synaptic potentials recorded from mammalian neurones prolonged by blockade of noradrenaline uptake. J Physiol. 1987 Jan;382:87–103. doi: 10.1113/jphysiol.1987.sp016357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Uchimura N., Higashi H., Nishi S. Hyperpolarizing and depolarizing actions of dopamine via D-1 and D-2 receptors on nucleus accumbens neurons. Brain Res. 1986 Jun 11;375(2):368–372. doi: 10.1016/0006-8993(86)90760-2. [DOI] [PubMed] [Google Scholar]
  13. White F. J., Wang R. Y. Electrophysiological evidence for the existence of both D-1 and D-2 dopamine receptors in the rat nucleus accumbens. J Neurosci. 1986 Jan;6(1):274–280. doi: 10.1523/JNEUROSCI.06-01-00274.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Williams J., Lacey M. Actions of cocaine on central monoamine neurons: intracellular recordings in vitro. NIDA Res Monogr. 1988;90:234–242. [PubMed] [Google Scholar]
  15. Wise R. A. Neural mechanisms of the reinforcing action of cocaine. NIDA Res Monogr. 1984;50:15–33. [PubMed] [Google Scholar]
  16. Woodruff G. N., McCarthy P. S., Walker R. J. Studies on the pharmacology of neurones in the nucleus accumbens of the rat. Brain Res. 1976 Oct 15;115(2):233–242. doi: 10.1016/0006-8993(76)90509-6. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES