Effects of ventral tegmental microinjections of the GABA(A) agonist muscimol on self-administration of ethanol and sucrose

Two groups of Long-Evans rats were trained to lever press on a fixed-ratio 4 (FR4) schedule of reinforcement with ethanol (10% v/v) or sucrose (75% w/v) presented as the reinforcer. After implantation of guide cannulae aimed at the ventral tegmental area (VTA), weekly bilateral injections of muscimol (10, 30, and 100 ng) were tested. During control conditions, response patterns for both groups were characterized by high rates that began shortly after the start of the session and terminated after approximately 10 min. Muscimol (10 ng) administration in the VTA increased the number of sucrose- but had no effect on the total number of ethanol-reinforced responses. Muscimol (30 ng) shifted the response patterns of both groups from high initial rates with early termination to slow initial rates with delayed termination, suggesting the possibility of nonspecific locomotor effects. These data suggest that ethanol- and sucrose-reinforced response totals are differentially sensitive to changes in GABAergic transmission in the VTA. The similar muscimol-induced changes in response patterns with the two reinforcers supports the hypothesis that GABA(A) receptors in the VTA are involved similarly in the maintenance of ethanol- and sucrose-reinforced responding. However, the failure of muscimol to increase ethanol-reinforced responding suggests that GABAergic systems in other brain regions may also be involved in the changes in ethanol intake seen following peripheral administration of GABAmimetic drugs.