GABA(A) and opioid receptors of the central nucleus of the amygdala selectively regulate ethanol-maintained behaviors.

The present study tested the hypothesis that GABA(A) and opioid receptors within the central nucleus of the amygdala (CeA) regulate ethanol (EtOH), but not sucrose-maintained responding. To accomplish this, betaCCt, a mixed benzodiazepine (BDZ) agonist-antagonist with binding selectivity at the alpha1 subunit-containing GABA(A) receptor, and the nonselective opioid antagonist, naltrexone, were bilaterally infused directly into the CeA of alcohol-preferring rats. The results demonstrated that in HAD-1 and P rat lines, betaCCt (5-60 microg) reduced EtOH-maintained responding by 56-89% of control levels. On day 2, betaCCt (10-40 microg) continued to suppress EtOH maintained responding in HAD-1 rats by as much as 60-85% of control levels. Similarly, naltrexone (0.5-30 microg) reduced EtOH-maintained responding by 56-75% of control levels in P rats. betaCCt and naltrexone exhibited neuroanatomical and reinforcer specificity within the CeA. Specifically, no effects on EtOH-maintained responding were observed following infusion into the caudate putamen (CPu), a locus several millimeters dorsal to the CeA. Additionally, responding maintained by sucrose, when presented concurrently with ethanol (EtOH) or presented alone, was not altered by betaCCt. Naltrexone reduced sucrose-maintained responding only under the 5 microg dose condition when sucrose was presented alone, however, it did not alter sucrose responding when given concurrently with EtOH. These results support the hypothesis that GABA(A) and opioid receptors within the CeA can selectively regulate EtOH-maintained responding. The CeA may represent a novel target site in the development of prototypical GABA(A) and opioidergic receptor ligands, which selectively reduce alcohol abuse in humans.