Background: Activation of GABA(A) receptors in the amygdala or nucleus accumbens produces discriminative stimulus effects that substitute fully for those of systemically administered ethanol. This study was conducted to determine if GABA(A) receptors in the amygdala and nucleus accumbens interactively modulate ethanol discrimination.
Methods: Male Long-Evans rats were trained to discriminate between intraperitoneal injections of ethanol (1 g/kg) and saline on a 2-lever drug discrimination task. The rats were then surgically implanted with bilateral injection cannulae aimed at the nucleus accumbens and the amygdala.
Results: Infusion of the GABA(A) agonist muscimol in the nucleus accumbens resulted in full substitution for systemically administered ethanol. Concurrent infusion of the GABA(A) antagonist bicuculline in the amygdala shifted the muscimol substitution curve in the nucleus accumbens 10-fold to the right.
Conclusions: These results indicate that blockade of GABA(A) receptors in the amygdala significantly reduces the potency of the GABA(A) agonist in the nucleus accumbens. This suggests that the ethanol-like stimulus effects of GABA(A) receptor activation in the nucleus accumbens are modulated by GABA(A) receptor activity in the amygdala. These data support the hypothesis that the addictive stimulus properties of alcohol are mediated by GABAergic transmission in a neural circuit involving the amygdala and nucleus accumbens.