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 hours 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.

Cue-elicited craving is modeled in rats using the conditioned place preference (CPP) paradigm, however it is not known whether this CPP produces a pattern of brain activations homologous to those reported in humans. To test the hypothesis that similar neural circuits underlie cueelicited craving in rodents and humans, we used behavioral neuroimaging with 2-[ 18 F]fluoro-2-deoxy-D-glucose (FDG) and positron emission tomography (PET) in freely moving rats during the expression of place preference to methamphetamine (METH). Statistical parametric mapping (SPM) correlated preference with regional changes in brain activation. We observed increased relative FDG uptake compared to baseline in the cerebellum, thalamus, frontal, sensory and motor cortices. There were significant decreases in the insular cortex and throughout the hippocampus. Covariate analysis revealed circuitry in the dorsal and ventral striatum, cingulate gyrus and amygdala where relative FDG uptake correlated with individual differences in preference. These findings demonstrate a strong overlap in those areas activated by the expression of place preference in rodents and distinct patterns of brain activation observed with expectancy and cue-induced craving in humans. We conclude that neuroimaging in animals enriches, and is enriched by, the field of Pavlovian conditioning as well as other fields of behavioral science.

Given the growing obesity epidemic, pressure to develop an effective pharmacologic treatment is mounting. Following the completion of a randomized, double-blind, placebo controlled trial as well as two small open label trials, gamma vinyl-GABA (GVG) has been shown to be safe and effective for treating cocaine and/or methamphetamine dependence. In an extension of these findings, the present study examined whether GVG could produce weight loss in adolescent as well as genetically obese animals. Specifically, adolescent Sprague Dawley and adolescent and adult Zucker fatty rats received GVG at various doses (75-300 mg/kg, i.p., racemic) for treatment periods lasting no longer than 14 consecutive days. GVG produced significant weight loss in a dose dependent fashion in all groups. These effects were marked, as average decreases of 12-20% of original body weight were observed. These findings suggest that GVG may be useful as a treatment for obesity. Further, that these results occurred in genetically obese animals offers the possibility that GVG may even help manage severe obesity resulting from binge-eating, a disorder involving food consumption in a pattern similar to the compulsive drug-seeking behavior observed in cocaine and methamphetamine dependent subjects.