γ-Aminobutyric acid mimetic drugs differentially inhibit the dopaminergic response to cocaine

Madina R. Gerasimov, Wynne K Schiffer, Jonathan D. Brodie, Ian C. Lennon, Stephen J.C. Taylor, Stephen L. Dewey

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Dopaminergic activity in the mesocorticolimbic system is associated with reinforcing properties of psychostimulant drugs. We previously demonstrated that increased γ-aminobutyric acid (GABA)-ergic activity produced by γ-vinyl GABA [D, L-4-amino-hex-5-enoic acid (Vigabatrin®)], an irreversible inhibitor of GABA-transaminase, attenuated cocaine, nicotine, heroin, alcohol, and methamphetamine-induced increases in extracellular nucleus accumbens dopamine as well as behaviors associated with these biochemical changes. In the present study, using in vivo microdialysis techniques, we compared three different strategies to increase GABAergic activity in order to modulate cocaine-induced increase in extracellular dopamine. Our data demonstrate that the anticonvulsant 1-(2-(((diphenylmethylene)amino)oxy)ethyl)-1,2,5,6-tetrahydro-3-pyridinecarboxylic acid hydrochloride (NNC-711), a GABA uptake inhibitor, dose and time dependently diminished increases in extracellular dopamine following acute cocaine challenge. Furthermore, we demonstrated that cyclized analogue of vigabatrin, a competitive reversible GABA-transaminase inhibitor, is a more potent inhibitor of cocaine-induced dopamine increase than vigabatrin. Our data suggest that in addition to irreversible inhibition of GABA transaminase, inhibition of GABA uptake represent another potentially effective, indirect strategy for the treatment of cocaine abuse.

Original languageEnglish (US)
Pages (from-to)129-135
Number of pages7
JournalEuropean Journal of Pharmacology
Volume395
Issue number2
DOIs
StatePublished - Apr 28 2000

Keywords

  • Cocaine
  • Dopamine
  • Microdialysis
  • γ-Aminobutyric acid (GABA)
  • γ-Aminobutyric acid (GABA) reuptake inhibitor
  • γ-Vinyl GABA (vigabatrin)

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    Gerasimov, M. R., Schiffer, W. K., Brodie, J. D., Lennon, I. C., Taylor, S. J. C., & Dewey, S. L. (2000). γ-Aminobutyric acid mimetic drugs differentially inhibit the dopaminergic response to cocaine. European Journal of Pharmacology, 395(2), 129-135. https://doi.org/10.1016/S0014-2999(00)00267-3