Behavioral activating effects of selective AMPA receptor antagonism in the ventral tegmental area.

In recent years, the role of glutamate in drug seeking has received increasing attention. The current study tested the hypothesis that NBQX (a selective AMPA receptor antagonist) in the ventral tegmental area (VTA) would reduce cocaine seeking. Rats were trained to lever-press for intravenous cocaine (1.0 mg/kg/injection). Two test conditions were used, each preceded by bilateral intra-VTA microinjections of vehicle, 0.5, 1.0 or 2.0 μg/0.5 μl of NBQX. In the without-conditioned-stimulus (without-CS) condition, neither active (cocaine-associated) nor inactive levers produced any consequences. In the with-CS condition, the active lever turned on the stimulus light (as during training) and the infusion pump, which delivered an injection of saline. NBQX produced 2 effects: (1) an overall increase in responding, and (2) an increase in active lever-pressing at the 0.5-μg dose in the with-CS condition. A separate group of rats was allowed to press 2 levers without reinforcement, and the 0.5-μg NBQX dose enhanced responding on both levers. These results failed to support the hypothesis that AMPA receptor antagonism in VTA would reduce cocaine seeking and suggest that such antagonism causes general activating effects and may enhance the capacity of cocaine-CSs to function as conditioned reinforcers.