Blocking GABAA receptors in the anterior ventral tegmental area attenuates ethanol intake of the alcohol-preferring P rat

The effect of blocking the A subtype of γ-aminobutyric acid (GABA_A)_{receptors in the anterior ventral tegmental area (VTA) on ethanol (EtOH; 10% v/v) and saccharin (SACC; 0.0125%) consumption was investigated in alcohol-preferring P rats. Picrotoxin (0.005, 0.01, 0.05 and 0.10 µg/0.5 µl) was injected into the VTA, and consumption of EtOH and SACC was assessed in two 2-h limited-access drinking paradigms (concurrent EtOH/ SACC access, and alternate-day-access to EtOH and SACC). Under concurrent-access conditions, the picrotoxin microinjections resulted in a 55 and 84% decrease in EtOH consumption at the 0.05 and 0.10 µg doses, respectively, compared with consumption following microinjections of vehicle solution (P<0.05). Saccharin intake was not significantly altered by picrotoxin. Under alternate-day-access drinking conditions, the picrotoxin microinjections resulted in dose-dependent decreases in EtOH consumption of 37–68%, with significant decreases following the 0.005, 0.05 and 0.10 µg doses (P<0.04). Saccharin intake was significantly reduced only at the 0.05 µg dose. The decrease in EtOH consumption after 0.10 µg picrotoxin was attenuated by co-administration of 0.01 µg muscimol. This dose of muscimol had no effect on EtOH consumption when injected alone. Intra-VTA injections of bicuculline (0.04 µg), another GABAA antagonist, reduced EtOH intake, comparable to the reduction following 0.10 µg picrotoxin. Microinjections of 0.10 µg picrotoxin in regions outside the VTA failed to decrease EtOH intake. These results suggest that anterior VTA mechanisms regulating alcohol drinking behavior are under tonic GABA inhibition, mediated by GABAA receptors. The results also suggest that different neural mechanisms are regulating voluntary EtOH and SACC drinking behaviors.}