Effects of GABAergic modulators on food and cocaine self-administration in baboons

Drugs that indirectly alter dopaminergic systems may alter the reinforcing effects of cocaine. The inhibitory neurotransmitter gamma-aminobutyric acid (GABA) has extensive neural connections in mesolimbic regions that appear to modulate dopamine. The current study evaluated the effects of GABA_B receptor agonists baclofen and CGP44532, the benzodiazepine agonist alprazolam, and the GABA reuptake inhibitor tiagabine on lever responding maintained by low dose cocaine injections (0.032 mg/kg) or by food pellet (1 g) delivery in baboons. The benzodiazepine antagonist flumazenil was tested as a negative control. Cocaine or food was available under a fixed ratio (FR 10) schedule of reinforcement during daily 2-h sessions. During baseline conditions, cocaine and pellets maintained similar numbers of reinforcers per session. Baclofen, CGP44532 and tiagabine dose-dependently reduced the number of cocaine injections, where as the benzodiazepine antagonist flumazenil did not. Baclofen, CGP44532 and tiagabine also produced dose-related decreases in food-maintained behavior. In contrast, the benzodiazepine agonist alprazolam, which positively modulates GABA_A receptors via the benzodiazepine site, produced decreases in cocaine self-injection, but not food-maintained behavior. Thus, the effects of alprazolam were specific for cocaine-maintained behavior, where as the effects of baclofen and CGP44532 were not.