Gamma-vinyl GABA inhibits methamphetamine, heroin, or ethanol-induced increases in nucleus accumbens dopamine.
We examined the acute effect of the irreversible GABA-transaminase inhibitor, gamma-vinyl GABA (GVG, Sabril((R)), Vigabatrin((R))) 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.
Gerasimov
M R
MR
Chemistry Department, Brookhaven National Laboratory, Upton, New York 11973, USA.
Ashby
C R
CR
Gardner
E L
EL
Mills
M J
MJ
Brodie
J D
JD
Dewey
S L
SL
D000701:Analgesics, Opioid / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002492:Central Nervous System Depressants / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004298:Dopamine / Q000134:cerebrospinal fluid / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000431:Ethanol / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D003932:Heroin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D008694:Methamphetamine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology
D000701:Analgesics, Opioid; D000927:Anticonvulsants; D002492:Central Nervous System Depressants; D018765:Dopamine Uptake Inhibitors; D000431:Ethanol; D008694:Methamphetamine; D005680:gamma-Aminobutyric Acid; D003932:Heroin; D020888:Vigabatrin; D004298:Dopamine