Oxytocin attenuates stress-induced reinstatement of alcohol seeking behavior in male and female mice

Abstract

Rationale: The neuropeptide oxytocin (OXT) has emerged as a potential therapeutic intervention in the treatment of both alcohol use disorder (AUD) and stress-related psychiatric illnesses. Objectives: The present study evaluates the effects of systemically administered (intraperitoneal (i.p.)) OXT treatment on alcohol relapse-like behavior in male and female mice. Methods: Adult male and female C57BL/6J mice were trained to lever respond in operant conditioning chambers for alcohol in daily self-administration sessions. Once lever responding and alcohol intake stabilized, mice were tested under extinction conditions for 14 days before reinstatement testing. All mice underwent stress-induced reinstatement testing using either predator odor (2,3,5-trimethyl-3-thiazoline (TMT)) or the α-2 adrenergic receptor agonist yohimbine. In study 1, mice were exposed to TMT for 15 min and then immediately placed into operant conditioning chambers to examine alcohol-seeking behavior under extinction conditions. At 30 min prior to test session, separate groups of mice were injected with vehicle or OXT (0.1, 0.5, 1 mg/kg). In study 2, mice were injected with yohimbine (0.3, 0.625 mg/kg) 1 h prior to reinstatement testing. At 30 min post-yohimbine injection, mice are injected (i.p.) with vehicle or OXT (1 mg/kg). Results: OXT attenuated alcohol-seeking behavior in a dose-related manner in male and female mice in response to acute challenge with a predator odor. Additionally, OXT administration produced a similar decrease in alcohol relapse-like behavior triggered by the pharmacological stressor yohimbine in both sexes. Conclusions: Systemic oxytocin administration attenuates stress-induced reinstatement of alcohol seeking in male and female mice.