Oxytocin significantly enhances GABAergic transmission in the central amygdala of alcohol-naïve and alcohol-dependent female rats.

Oxytocin is a promising treatment for alcohol use disorder (AUD) and has been shown to decrease alcohol consumption and withdrawal symptoms associated with alcohol dependence in animal models. Using a rat model of alcohol dependence to investigate oxytocin's effects on dependence-induced alcohol drinking and GABAergic transmission in the central amygdala (CeA), we previously reported that oxytocin blocked escalated alcohol drinking and the acute ethanol-induced enhanced GABA transmission in alcohol-dependent rats. However, these studies were performed only in male rats. We also previously reported sex differences in the effects of alcohol and stress related neuropeptides on CeA GABAergic transmission. Here we examined the effects of oxytocin on CeA GABAergic transmission in naïve and alcohol-dependent female rats, as well as examining sex differences in the expression of components of the oxytocin system. We found that oxytocin increased CeA GABAergic transmission in both naive and alcohol-dependent female rats and this increase was further elevated after the co-application of acute alcohol. We also found that females had fewer oxytocin-expressing neurons in the caudal paraventricular nucleus of the hypothalamus than males, and alcohol-dependent rats had fewer oxytocin-expressing neurons than naïve rats. Further, females had higher numbers of corticotropin releasing factor (Crh) neurons in the CeA, and higher expression levels of Crh and oxytocin receptor mRNA. This research highlights sex differences in pro- and anti-stress system functioning in the CeA in response to acute and chronic alcohol. Sex-specific neuroadaptations in oxytocin signaling may provide a target for more effective therapeutics in the treatment of AUD.