The irreversible gamma-aminobutyric acid (GABA) transaminase inhibitor gamma-vinyl-GABA blocks cocaine self-administration in rats

gamma-Vinyl gamma-aminobutyric acid (GABA) (GVG) is an irreversible inhibit or of GABA transaminase, the primary enzyme involved in GABA metabolism. Ac ute administration of GVG increases brain GABA levels and blocks cocaine-in duced locomotor activity, cocaine-induced lowering of brain stimulation rew ard thresholds, and cocaine-induced conditioned place preference. To furthe r evaluate the effects of GVG on cocaine-induced reward, we examined its ef fects on cocaine self-administration in male Wistar rats on fixed ratio 5 a nd progressive ratio schedules of reinforcement. Additionally, the effects of GVG on operant responding for a food reward were examined on the same tw o schedules to determine whether the effects of GVG were specific to cocain e reward or generalized to other types of reward. GVG dose dependently decr eased responding for cocaine on both schedules of reinforcement, suggesting that GVG attenuated the reward value of the cocaine. Responding for food w as also decreased by GVG, suggesting that the effects of increased GABA lev els induced by GVG may have a general effect on central reward systems. Dat a from this and other studies indicate that GVG does not induce motor impai rment, decrease spontaneous locomotor activity, or induce catalepsy. Taken together, these data suggest that increases in GABAergic activity induced b y GVG have an attenuating effect on centrally mediated reward systems and t hat the GABA system may be a useful target in the development of new therap eutic strategies for cocaine addiction.