Abstract
Alcohol use disorders (AUDs) are significant public health concerns, characterized by compulsive seeking and consumption of alcohol. AUDs have been linked to disruption of normal functioning of brain stress systems, as the transition to dependence recruits these systems leading to the negative affective states seen in withdrawal; the relief of which drives further drinking. The central nucleus of the amygdala (CeA) functions as a neuropeptidergic hub of stress and anxiety processing, and GABAergic signaling within the CeA is involved in the regulation of alcohol consumption. Oxytocin is a stress‐related neuropeptide that has previously been shown to alter GABAergic signaling within the CeA of rodents. Oxytocin also affects alcohol addiction, dependence, and withdrawal, as administration of oxytocin decreases drinking and blocks alcohol withdrawal symptoms in humans and rodents. However, characterization of the electrophysiological effects of oxytocin and alcohol on GABAergic signaling in the CeA have not yet been reported. In this study, we used whole cell patch clamp electrophysiological recordings to examine the effects of oxytocin and alcohol on CeA GABAergic signaling in both alcohol naïve and chronic intermittent alcohol vapor treated (alcohol dependent) Sprague‐Dawley male and female rats. We also used immunohistochemical staining to identify alcohol dependence induced changes in oxytocin expression in male and female rats. Oxytocin decreased sIPSC amplitudes in both naïve and dependent male animals, but blocked alcohol‐induced enhancement of sIPSC frequency in dependents only, indicating both pre‐ and post‐synaptic effects of oxytocin on GABAergic transmission. Pretreatment with an oxytocin antagonist blocked the effects of oxytocin and restored the alcohol enhancement in sIPSC frequency. In female naïve rats, oxytocin has no effects on sIPSCs alone, and does not block the alcohol enhancement of sIPSC frequency, but in alcohol dependent females, oxytocin increases sIPSC frequency alone and additional alcohol increases sIPSC frequency even further. These results provide important insight into the role of oxytocin in CeA neuronal functioning and the sexually dimorphic changes in this system that contributes to the transition to alcohol dependence. This research highlights the potential role of oxytocin in the development of novel targeted therapeutics for the effective treatment of AUDs.Support or Funding InformationNIH/NIAAA F32: AA025262, T32: AA007456, R01: AA017447, AA006420, AA015566This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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