Gamma-vinyl GABA inhibits cocaine-triggered reinstatement of drug-seeking behavior in rats by a non-dopaminergic mechanism.
Relapse to drug use is a core feature of addiction. Previous studies demonstrate that gamma-vinyl GABA (GVG), an irreversible GABA transaminase inhibitor, attenuates the acute rewarding effects of cocaine and other addictive drugs. We here report that systemic administration of GVG (25-300 mg/kg) dose-dependently inhibits cocaine- or sucrose-induced reinstatement of reward-seeking behavior in rats. In vivo microdialysis data indicated that the same doses of GVG dose-dependently elevate extracellular GABA levels in the nucleus accumbens (NAc). However, GVG, when administered systemically or locally into the NAc, failed to inhibit either basal or cocaine-priming enhanced NAc dopamine in either naïve rats or cocaine extinction rats. These data suggest that: (1) GVG significantly inhibits cocaine- or sucrose-triggered reinstatement of reward-seeking behavior; and (2) a GABAergic-, but not dopaminergic-, dependent mechanism may underlie the antagonism by GVG of cocaine-triggered reinstatement of drug-seeking behavior, at least with respect to GVG's action on the NAc.
Neuropsychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, DHHS, Baltimore, MD 21224, United States.
Xiao-Qing
XQ
Peng
Xia
X
Li
Jeremy G
JG
Gilbert
Arlene C
AC
Pak
Charles R
CR
Ashby
Jonathan D
JD
Brodie
Stephen L
SL
Dewey
Eliot L
EL
Gardner
Zheng-Xiong
ZX
Xi
D000818:Animals; D016739:Behavior, Addictive / Q000517:prevention & control*; D001522:Behavior, Animal / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D003042:Cocaine / Q000008:administration & dosage*; D004298:Dopamine / Q000378:metabolism*; D005106:Exploratory Behavior / Q000187:drug effects*; D005108:Extinction, Psychological / Q000187:drug effects*; D018682:GABA Agents / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D012201:Reward; D012646:Self Administration; D020888:Vigabatrin / Q000008:administration & dosage / Q000494:pharmacology*
D018682:GABA Agents; D020888:Vigabatrin; D003042:Cocaine; D004298:Dopamine