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.
Peng
Xiao-Qing
XQ
Neuropsychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, DHHS, Baltimore, MD 21224, United States.
Li
Xia
X
Gilbert
Jeremy G
JG
Pak
Arlene C
AC
Ashby
Charles R
CR
Brodie
Jonathan D
JD
Dewey
Stephen L
SL
Gardner
Eliot L
EL
Xi
Zheng-Xiong
ZX
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