Premium
Gamma‐vinyl GABA inhibits methamphetamine, heroin, or ethanol‐induced increases in nucleus accumbens dopamine
Author(s) -
Gerasimov Madina R.,
Ashby Charles R.,
Gardner Eliot L.,
Mills Mark J.,
Brodie Jonathan D.,
Dewey Stephen L.
Publication year - 1999
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/(sici)1098-2396(199910)34:1<11::aid-syn2>3.0.co;2-5
Subject(s) - nucleus accumbens , methamphetamine , pharmacology , chemistry , dopamine , ethanol , biochemistry , endocrinology , medicine
Abstract We examined the acute effect of the irreversible GABA‐transaminase inhibitor, gamma‐vinyl GABA (GVG, Sabril ® , Vigabatrin ® ) on increases in nucleus accumbens (NAc) dopamine (DA) following acute administration of methamphetamine, heroin, or ethanol. Methamphetamine (2.5 mg/kg) produced a dose‐dependent increase (2,700%) in NAc DA. GVG preadministration (300 or 600 mg/kg), however, inhibited this response by approximately 39 and 61%, respectively. The lower dose of methamphetamine (1.25 mg/kg), increased DA by 1,700%. This response was inhibited to a similar extent (44%) regardless of the GVG dose preadministered (300 or 600 mg/kg). In addition, heroin‐induced increases in NAc DA (0.5 mg/kg, 170%) were inhibited or completely abolished by GVG (150 or 300 mg/kg, 65 and 100%, respectively). Finally, at half the dose necessary for heroin, GVG (150 mg/kg) also completely abolished ethanol‐induced increases in NAc DA following a 0.25 g/kg challenge dose (140%). Taken with our previous findings using nicotine or cocaine as the challenge drug, these results indicate that GVG attenuates increases in NAc DA by a mechanism common to many drugs of abuse. However, it appears unlikely that an acute dose of GVG can completely inhibit increases in NAc DA following challenges with a drug whose mechanism of action is mediated primarily through the DA reuptake site. Synapse 34:11–19, 1999. © 1999 Wiley‐Liss, Inc.