| gamma-aminobutyric acid mimetic drugs differentially inhibit the dopaminergic response to cocaine. | |
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MedLine Citation:
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PMID: 10794818 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Dopaminergic activity in the mesocorticolimbic system is associated with reinforcing properties of psychostimulant drugs. We previously demonstrated that increased gamma-aminobutyric acid (GABA)-ergic activity produced by gamma-vinyl GABA [D,L-4-amino-hex-5-enoic acid (Vigabatrin(R))], 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. |
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Authors:
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M R Gerasimov; W K Schiffer; J D Brodie; I C Lennon; S J Taylor; S L Dewey |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: European journal of pharmacology Volume: 395 ISSN: 0014-2999 ISO Abbreviation: Eur. J. Pharmacol. Publication Date: 2000 Apr |
Date Detail:
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Created Date: 2000-09-06 Completed Date: 2000-09-06 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: NETHERLANDS |
Other Details:
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Languages: eng Pagination: 129-35 Citation Subset: IM |
Affiliation:
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Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973-5000, USA. madina@bnl.gov |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cocaine / administration & dosage, antagonists & inhibitors*, pharmacology Dopamine Uptake Inhibitors / administration & dosage, pharmacology* Dose-Response Relationship, Drug Drug Administration Schedule GABA Antagonists / pharmacology Male Microdialysis Molecular Mimicry Nipecotic Acids / pharmacology Oximes / pharmacology Rats Rats, Sprague-Dawley Receptors, Dopamine / drug effects, metabolism* Sodium Chloride gamma-Aminobutyric Acid / analogs & derivatives*, metabolism, pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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MH49165/MH/NIMH NIH HHS; R2955155//PHS HHS |
| Chemical | |
Reg. No./Substance:
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0/Dopamine Uptake Inhibitors; 0/GABA Antagonists; 0/Nipecotic Acids; 0/Oximes; 0/Receptors, Dopamine; 145645-62-1/NNC 711; 50-36-2/Cocaine; 56-12-2/gamma-Aminobutyric Acid; 7647-14-5/Sodium Chloride |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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