AUTHOR=Alper Kenneth , Cange Janelle , Sah Ria , Schreiber-Gregory Deanna , Sershen Henry , Vinod K. Yaragudri 

TITLE=Psilocybin sex-dependently reduces alcohol consumption in C57BL/6J mice

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 13 - 2022

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.1074633

DOI=10.3389/fphar.2022.1074633

ISSN=1663-9812

ABSTRACT=The classical psychedelic psilocybin is of interest as a treatment for alcohol use disorder (AUD). This study investigated the effects of psilocybin on voluntary alcohol consumption in adult male and female C57BL/6J mice administered saline or psilocybin intraperitoneally as a single dose of 0.1, 0.5, 1.0 or 2.0 mg/kg and provided 20% ethanol utilizing a two-bottle choice alcohol drinking paradigm. Alcohol was provided continuously for three days immediately following the administration of psilocybin, then withheld for two days, and then provided continuously for two subsequent additional days. A multilevel model (MLM) for repeated measures was used to compare alcohol consumption and preference in psilocybin-treated groups versus controls. 

Alcohol consumption and preference were reduced in male mice during the three-day interval that immediately followed psilocybin administration. The effect of psilocybin on alcohol consumption was dose-related and was consistent across the three-day interval at dosages of 0.5mg/kg greater. Psilocybin had no effect on consumption or preference in males when alcohol was subsequently reintroduced after it had been withheld for two days. In contrast to males, psilocybin had no significant effect on alcohol consumption or preference in female mice at any dosage or time point. The lack of an effect of psilocybin on quinine preference, and its limited interaction with locomotor activity indicated that the observed reduction in voluntary alcohol consumption was not attributable to altered taste perception or motor effects. The finding of a sex-dependent effect of psilocybin suggests that the C57BL/6J mouse may provide a useful experimental approach to modeling sex differences in vulnerability to AUD in addition to investigation of the neurobiological basis of the effect of classical psychedelics on alcohol drinking behavior.