title: Gamma-vinyl GABA, an irreversible inhibitor of GABA transaminase, alters the acquisition and expression of cocaine-induced sensitization in male rats.
abstract: We examined the effect of (+/-)-gamma-vinyl GABA (GVG, Vigabatrin), an irreversible inhibitor of the enzyme GABA transaminase, on the acquisition and expression of cocaine-induced sensitization in albino male Sprague-Dawley rats. Animals received a single injection of 1 ml/kg i.p. of 0.9% saline or 15 mg/kg i.p. of (-)-cocaine and locomotor activity was assessed using automated locomotor cages and stereotyped behaviors were scored using a 4-point rating scale (Day 1). Subsequently, animals were given 15 mg/kg i.p. of cocaine every 48 h in their home cage for 1 week (Days 3, 5, and 7) and then given no treatment for 1 week. A challenge injection of 15 mg/kg i.p. of cocaine, but not vehicle, produced a significant increase in locomotor activity and stereotyped behaviors on Day 15 compared to animals that received cocaine on Day 1. Administration of 75 mg/kg i.p. of GVG 2.5 h before the cocaine injections did not significantly alter the acquisition of cocaine-induced locomotor sensitization. However, 150 mg/kg i.p. of GVG significantly attenuated the acquisition of cocaine-induced locomotor sensitization. Administration of 150 mg/kg i.p. of GVG 2.5 h before the cocaine challenge injection on Day 15 significantly attenuated the expression of cocaine-induced locomotor sensitization. Acquisition and expression of cocaine-induced sensitization of stereotypy was also significantly attenuated by 150 mg/kg i.p. of GVG. Since sensitization may be one of the factors involved in relapse to drug use, the present results, in combination with previous findings that GVG blocks the rewarding and incentive motivating effects of cocaine, suggest that GVG might prove useful in the treatment of cocaine addiction.
authors.affiliation: Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, Maryland 21224, USA.
authors.forename: Eliot L
authors.initials: EL
authors.lastname: Gardner
authors.forename: Wynne K
authors.initials: WK
authors.lastname: Schiffer
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Horan
authors.forename: David
authors.initials: D
authors.lastname: Highfield
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Dewey
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Brodie
authors.forename: Charles R
authors.initials: CR
authors.lastname: Ashby
mesh_terms: D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D016739:Behavior, Addictive / Q000188:drug therapy / Q000201:enzymology; D003042:Cocaine / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013239:Stereotyped Behavior / Q000187:drug effects* / Q000502:physiology; D020888:Vigabatrin / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000612:4-Aminobutyrate Transaminase; D020888:Vigabatrin; D003042:Cocaine