Conditioned social preference and reward value of activating oxytocin‐receptor‐expressing ventral tegmental area neurons following repeated daily binge ethanol intake

Background

Patients with alcohol use disorder (AUD) exhibit disruption of social behavior and dysregulation of oxytocin signaling in the brain, possibly reflecting decreased activation of oxytocin receptors (OxTR) in reward pathways in response to social stimuli. We hypothesize that daily binge ethanol intake causes a deficit in social reward and oxytocin signaling in the ventral tegmental area (VTA).

Methods

After 9 weeks of daily binge ethanol intake (blood ethanol >80 mg%), OxTR-cre mice underwent conditioned place preference for social reward. Separate groups of mice were tested for effects of binge ethanol on voluntary social interactions as well as food reward, locomotion, and anxiety-like behaviors. Finally, a subset of mice underwent transfection of OxTR-expressing VTA neurons (VTAOxtr) with a light-sensitive opsin, followed by training to operantly respond to light delivered to VTA.

Results

Ethanol-naïve male mice increased time spent on the side previously paired with novel mice while ethanol-treated mice did not. Binge ethanol did not affect conditioned place preference for food reward in males, but this response was weakened in ethanol-treated females. Ethanol treatment also caused sex-specific impairment of voluntary social interactions with novel mice. There were minimal differences between groups in measures of anxiety and locomotion. Ethanol-naïve mice had significantly increased operant responding for activation of VTAOxtr compared to sham-transfected mice but ethanol-treated mice did not. There was no difference in the number of VTAOxtr after binge ethanol.

Conclusions

Daily binge ethanol causes social reward deficits that can’t be explained by non-specific effects on other behaviors, at least in males. Only ethanol-naïve mice exhibited positive reinforcement caused by activation of VTAOxtr while daily binge ethanol did not alter the number of VTAOxtr in either males or females. Thus, subtle dysregulation of VTAOxtr function may be related to the social reward deficits caused by daily binge ethanol.

留言 (0)

沒有登入
gif