Selective effects of oxytocin on alcohol drinking in subpopulations of male and female mice following intermittent predator stress.

Abstract

Aims: Excessive alcohol use is often triggered by traumatic experiences, when subjects consume alcohol-containing beverages as a passive coping mechanism to relieve negative affect. There are no FDA-approved medications that are specifically recommended for patients with alcohol use disorder who use alcohol to decrease the consequences of trauma. The current study used a mouse model of predator stress-enhanced drinking to test whether administration of oxytocin (OXT) could selectively target subjects with increased sensitivity to psychological trauma.

Methods: Male and female C57BL/6J mice established consumption of 10% ethanol in a 2-bottle choice procedure and then were exposed to predator odor (soiled rat bedding) during four intermittent 30-minute sessions. Mice were designated as Sensitive, increasing ethanol intake, or Resilient, showing no increases in intake, following the predator odor exposures. Effects of OXT (1 mg/kg) on ethanol intake were examined at two and at four hours following treatment using an automated lickometer system.

Results: OXT non-selectively decreased ethanol and water intake in male and female mice during the first two hours after administration, suggesting sedative effects. Importantly, when analyzed at four hours post-injection, OXT selectively decreased ethanol, but not water intake, in male mice and in the Sensitive subgroup of female mice and had no significant effects on ethanol intake in the Resilient female mice.

Conclusions: These results indicate that the predator odor model can help screen for pharmacotherapies to treat patients consuming alcohol to passively cope with trauma-induced negative affect. Further studies need to test whether OXT is preferentially effective in such subjects.