Home LiteratureArticle Details
PMID: 2361170 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Actions of cocaine on rat dopaminergic neurones in vitro.

British journal of pharmacology ·Vol. 99 ·No. 4 ·1990-04-00 ·Pages 731-5

Lacey MG, Mercuri NB, North RA

Abstract

1. Intracellular recordings were made from neurones in vitro in the rat substantia nigra zona compacta and ventral tegmental area; the neurones had the characteristic properties of dopamine-containing cells, and fired action potentials spontaneously. 2. Cocaine (1-10 microM) inhibited spontaneous firing, hyperpolarized the membrane and (in neurones voltage-clamped at -60 mV) caused an outward membrane current; the minimally effective concentration was 1 microM. These effects were blocked by sulpiride (30 nM-1 microM). 3. Dopamine (3-100 microM) also inhibited firing, hyperpolarized and caused an outward current. These effects of dopamine were potentiated about five fold by cocaine (10 microM). 4. It is concluded that cocaine (1-10 microM) inhibits the firing and hyperpolarizes substantia nigra zona compacta neurones in vitro by blocking the uptake of dopamine which the cells continuously release.

MeSH Terms
Action Potentials/drug effects Animals Cocaine/pharmacology Dopamine/pharmacology,physiology In Vitro Techniques Microelectrodes Neurons/drug effects,metabolism Rats Substantia Nigra/drug effects Sulpiride/pharmacology Tetrodotoxin/pharmacology
Chemicals
Tetrodotoxin Sulpiride Cocaine Dopamine
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Lacey M G
Vollum Institute, Oregon Health Sciences University, Portland 97201.
Mercuri N B
North R A
References (32)
32 references, click to expand
  1. Comparison of effects of L-dopa, amphetamine and apomorphine on firing rate of rat dopaminergic neurones.
    Nat New Biol. 1973 Sep 26;245(143):123-5 PMID: 4518113
  2. Actions of cocaine on rat nucleus accumbens neurones in vitro.
    Br J Pharmacol. 1990 Apr;99(4):736-40 PMID: 2193689
  3. Self-inhibition by dopaminergic neurons.
    Science. 1975 Nov 7;190(4214):522-8 PMID: 242074
  4. Studies on the pharmacology of neurones in the nucleus accumbens of the rat.
    Brain Res. 1976 Oct 15;115(2):233-42 PMID: 184877
  5. Drugs and reinforcement mechanisms: a critical review of the catecholamine theory.
    Annu Rev Pharmacol Toxicol. 1978;18:37-56 PMID: 348064
  6. Cocaine plasma concentration: relation to physiological and subjective effects in humans.
    Science. 1978 Oct 13;202(4364):227-8 PMID: 694530
  7. Dopamine release from the rat substantia nigra in vitro. Effect of raphe lesions and veratridine stimulation.
    Neuroscience. 1979;4(12):2021-9 PMID: 530442
  8. Presynaptic receptors.
    Annu Rev Pharmacol Toxicol. 1981;21:7-30 PMID: 6263176
  9. Disruption of cocaine self-administration following 6-hydroxydopamine lesions of the ventral tegmental area in rats.
    Pharmacol Biochem Behav. 1982 Nov;17(5):901-4 PMID: 6817350
  10. Cocaine: comparative effect on dopamine uptake in extrapyramidal and limbic systems.
    Biochem Pharmacol. 1983 Feb 15;32(4):744-6 PMID: 6830639
  11. Sodium-sensitive cocaine binding to rat striatal membrane: possible relationship to dopamine uptake sites.
    J Neurochem. 1983 Jul;41(1):172-8 PMID: 6864217
  12. Intracellular and extracellular electrophysiology of nigral dopaminergic neurons--2. Action potential generating mechanisms and morphological correlates.
    Neuroscience. 1983 Oct;10(2):317-31 PMID: 6633864
  13. Neural mechanisms of the reinforcing action of cocaine.
    NIDA Res Monogr. 1984;50:15-33 PMID: 6440023
  14. Dopamine uptake is differentially regulated in rat striatum and nucleus accumbens.
    J Neurochem. 1985 Jul;45(1):51-6 PMID: 3998732
  15. Sodium dependent [3H]cocaine binding associated with dopamine uptake sites in the rat striatum and human putamen decrease after dopaminergic denervation and in Parkinsons disease.
    Naunyn Schmiedebergs Arch Pharmacol. 1985 May;329(3):227-35 PMID: 3927176
  16. 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):274-80 PMID: 2868077
  17. Hyperpolarizing and depolarizing actions of dopamine via D-1 and D-2 receptors on nucleus accumbens neurons.
    Brain Res. 1986 Jun 11;375(2):368-72 PMID: 2942222
  18. High-affinity [3H]GBR 12783 binding to a specific site associated with the neuronal dopamine uptake complex in the central nervous system.
    Eur J Pharmacol. 1986 Jul 31;126(3):211-22 PMID: 3489625
  19. Detecting behaviorally relevant changes in extracellular dopamine with microdialysis.
    Brain Res. 1987 Jun 2;412(2):397-9 PMID: 3607474
  20. Inhibitory synaptic potentials recorded from mammalian neurones prolonged by blockade of noradrenaline uptake.
    J Physiol. 1987 Jan;382:87-103 PMID: 3625561
  21. Cocaine receptors on dopamine transporters are related to self-administration of cocaine.
    Science. 1987 Sep 4;237(4819):1219-23 PMID: 2820058
  22. Electrophysiological effects of cocaine in the mesoaccumbens dopamine system: studies in the ventral tegmental area.
    J Neurosci. 1988 Jan;8(1):100-12 PMID: 3339402
  23. Dopamine acts on D2 receptors to increase potassium conductance in neurones of the rat substantia nigra zona compacta.
    J Physiol. 1987 Nov;392:397-416 PMID: 2451725
  24. Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats.
    Proc Natl Acad Sci U S A. 1988 Jul;85(14):5274-8 PMID: 2899326
  25. On the potassium conductance increase activated by GABAB and dopamine D2 receptors in rat substantia nigra neurones.
    J Physiol. 1988 Jul;401:437-53 PMID: 2459376
  26. Cellular and molecular mechanisms of drug dependence.
    Science. 1988 Nov 4;242(4879):715-23 PMID: 2903550
  27. Extracellular cocaine and dopamine concentrations are linearly related in rat striatum.
    Brain Res. 1988 Jul 26;456(2):317-23 PMID: 3208083
  28. Two cell types in rat substantia nigra zona compacta distinguished by membrane properties and the actions of dopamine and opioids.
    J Neurosci. 1989 Apr;9(4):1233-41 PMID: 2703874
  29. Enhancement of dopamine actions on rat nucleus accumbens neurones in vitro after methamphetamine pre-treatment.
    J Physiol. 1989 Jan;408:587-603 PMID: 2550628
  30. Differential actions of cocaine and amphetamine on dorsal raphe neurons in vitro.
    J Pharmacol Exp Ther. 1989 Oct;251(1):56-62 PMID: 2795470
  31. Actions of cocaine on central monoamine neurons: intracellular recordings in vitro.
    NIDA Res Monogr. 1988;90:234-42 PMID: 3151928
  32. Studies on the distinction between uptake inhibition and release of (3H)dopamine in rat brain tissue slices.
    Biochem Pharmacol. 1975 Apr 15;24(8):847-52 PMID: 1125084
Article Info
Journal
British journal of pharmacology
Abbr.
Br J Pharmacol
ISSN
0007-1188
DOI
10.1111/j.1476-5381.1990.tb12998.x
Published
1990-04-00
Pages
731-5
Language
English
Region
England
NLM ID
7502536
PMCID
PMC1917549
Subset
IM
Grants
NIDA NIH HHS · DA03160 · United States
NIDA NIH HHS · DA03161 · United States
NIMH NIH HHS · MH40416 · United States
External Links
PubMed source DOI: 10.1111/j.1476-5381.1990.tb12998.x PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2