title: Racemic gamma vinyl-GABA (R,S-GVG) blocks methamphetamine-triggered reinstatement of conditioned place preference.
abstract: Preventing relapse poses a significant challenge to the successful management of methamphetamine (METH) dependence. Although no effective medication currently exists for its treatment, racemic gamma vinyl-GABA (R,S-GVG, vigabatrin) shows enormous potential as it blocks both the neurochemical and behavioral effects of a variety of drugs, including METH, heroin, morphine, ethanol, nicotine, and cocaine. Using the reinstatement of a conditioned place preference (CPP) as an animal model of relapse, the present study specifically investigated the ability of an acute dose of R,S-GVG to block METH-triggered reinstatement of a METH-induced CPP. Animals acquired a METH CPP following a 20-day-period of conditioning, in which they received 10 pairings of alternating METH and saline injections. During conditioning, rats were assigned to one of four METH dosage groups: 1.0, 2.5, 5.0, or 10.0 mg/kg (i.p., n = 8/group). Animals in all dosage groups demonstrated a robust and consistent CPP. This CPP was subsequently extinguished in each dosage group with repeated saline administration. Upon extinction, all groups reinstated following an acute METH challenge. On the following day, an acute dose of R,S-GVG (300 mg/kg, i.p.) was administered 2.5 h prior to an identical METH challenge. R,S-GVG blocked METH-triggered reinstatement in all four groups. Given that drug re-exposure may potentiate relapse to drug-seeking behavior, the ability of R,S-GVG to block METH-triggered reinstatement offers further support for its use in the successful management of METH dependence.
authors.affiliation: Medical Department, Brookhaven National Laboratory, Upton, New York 11973, USA. ald2126@columbia.edu
authors.forename: Amy
authors.initials: A
authors.lastname: DeMarco
authors.forename: Reema M
authors.initials: RM
authors.lastname: Dalal
authors.forename: Jessica
authors.initials: J
authors.lastname: Pai
authors.forename: Stefanie D
authors.initials: SD
authors.lastname: Aquilina
authors.forename: Uma
authors.initials: U
authors.lastname: Mullapudi
authors.forename: Crystie
authors.initials: C
authors.lastname: Hammel
authors.forename: Shiva K
authors.initials: SK
authors.lastname: Kothari
authors.forename: Milan
authors.initials: M
authors.lastname: Kahanda
authors.forename: Courtney N B
authors.initials: CN
authors.lastname: Liebling
authors.forename: Vinal
authors.initials: V
authors.lastname: Patel
authors.forename: Wynne K
authors.initials: WK
authors.lastname: Schiffer
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Brodie
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Dewey
mesh_terms: D019969:Amphetamine-Related Disorders / Q000517:prevention & control*; D000818:Animals; D000697:Central Nervous System Stimulants / Q000009:adverse effects*; D003214:Conditioning, Classical / Q000187:drug effects; D005108:Extinction, Psychological / Q000187:drug effects; D018682:GABA Agents / Q000494:pharmacology*; D007536:Isomerism; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012008:Recurrence; D020888:Vigabatrin / Q000494:pharmacology*
chemical_list: D000697:Central Nervous System Stimulants; D018682:GABA Agents; D008694:Methamphetamine; D020888:Vigabatrin