Voluntary alcohol consumption is increased in female, but not male, oxytocin receptor knockout mice

Abstract

Introduction: The oxytocin (Oxt) system, while typically associated with the neural regulation of social behaviors, also plays a role in an individual's vulnerability to develop alcohol use disorders (AUD). In humans, changes to the Oxt system, due to early life experience and/or genetic mutations, are associated with increased vulnerability to AUD. While a considerable amount is known about Oxt's role in AUD in males, less is known or understood, about how Oxt may affect AUD in females, likely due to many clinical and preclinical studies of AUD not directly considering sex as a biological variable. This is unfortunate given that females are more vulnerable to the effects of alcohol and have increased alcohol consumption, as compared to males. Therefore, in the current study we wanted to determine whether genetic disruption of the Oxt receptor (Oxtr), that is, Oxtr knockout (-/-) mice, affected stress-induced alcohol consumption in males and females. We hypothesized that genetic disruption of the Oxtr would result in increased stress-induced alcohol consumption in both males and females compared to wild-type (+/+) controls. Though, we predicted that these disruptions might be greater in female Oxtr -/- mice.

Methods: To test this hypothesis, a two-bottle preference test was utilized along with the forced swim test (FST), and pre- and poststress alcohol consumption and preference measured within each sex (males and females were run separately). As a follow-up experiment, a taste preference test, to control for possible genotypic differences in taste, was also performed.

Results: In males, we found no significant genotypic differences in alcohol consumption or preference. However, in females, we found that genetic disruption of the Oxtr resulted in a greater consumption of alcohol both pre- and poststress compared to controls.

Conclusion: These data suggest that in females, disruptions in Oxt signaling may contribute to increased vulnerability to alcohol-associated addiction.

Keywords: forced swim test; knockout mice; oxytocin; oxytocin receptor; voluntary alcohol consumption.