GABA(A) receptors in the dorsal raphé nucleus of mice: escalation of aggression after alcohol consumption.

Abstract

The dorsal raphé nucleus (DRN), the origin for serotonin (5-HT) in forebrain areas, has been implicated in the neural control of escalated aggression. Gamma aminobutyric acid type-A (GABA(A)) and type-B (GABA(B)) receptors are expressed in the DRN and modulate 5-HT neuronal activity, and both play a role in the behavioral effect of alcohol. The purpose of this study is to examine the interaction between drugs acting on GABA receptors in the DRN and alcohol in their effects on aggressive behaviors. Male CFW mice, housed with a female, were trained to self-administer ethanol (1.0 g/kg) or water via an operant conditioning panel in their home cage. Immediately after they drank either ethanol or water, the animals were microinfused with a GABAergic drug into the DRN, and their aggressive behaviors were assessed 10 min later. Muscimol (0.006 nmol), a GABA(A) receptor agonist, escalated alcohol-heightened aggression but had no effect in the absence of ethanol. This effect of muscimol was prominent in the animals that showed alcohol-heightened aggression, but not the animals that reduced or did not change aggressive behavior after ethanol infusion compared to water. On the other hand, the GABA(B) agonist baclofen (0.06 nmol) increased aggressive behavior similarly in both water and ethanol conditions. Antagonists of the GABA(A) and GABA(B) receptors, bicuculline (0.006 nmol) and phaclofen (0.3 nmol) respectively, did not suppress heightened-aggressive behavior induced by ethanol self-administration. GABA(A) receptors in the DRN are one of the neurobiological targets of alcohol-heightened aggression. Activation of the GABA(B) receptors in the DRN also produced escalated aggression, but that is independent of the effect of alcohol.