GABAA and Opioid Receptors of the Central Nucleus of the Amygdala Selectively Regulate Ethanol-Maintained Behaviors

Abstract

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, CCt, a mixed benzodiazepine (BDZ) agonist–antagonist with binding selectivity at the 1 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, CCt (5–60 g) reduced EtOH-maintained responding by 56–89% of control levels. On day 2, CCt (10–40 g) continued to suppress EtOH maintained responding in HAD-1 rats by as much as 60–85% of control levels. Similarly, naltrexone (0.5–30 g) reduced EtOH-maintained responding by 56–75% of control levels in P rats. CCt 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 CCt. Naltrexone reduced sucrose-maintained responding only under the 5 g 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.