부산대학교 도서관

Cannabinoids and their principle psychoactive target, the cannabinoid type 1 receptor (CB1R), impact a number of alcohol‐related properties, and although alcohol and cannabis are often co‐used, particularly in adolescence, few animal models of this phenomenon exist. We modeled the co‐use of alcohol and ∆9‐tetrahydrocannabinol (THC) in adolescent mice using ingestive methods popular during this developmental period in humans, namely binge‐drinking and edible THC. With this model, we assessed levels of use, acute effects, and tolerance to each substance. Adolescent male C57BL/6J mice had daily, limited access to 1 of 2 edible doughs (THCor control), to 1 of 2 fluids (ethanol (EtOH) or water), and in 1 of 2 orders (dough–fluid or fluid–dough). Home cage locomotor activity was recorded both during access and after access. On the day following the final access session, a subset of mice were assessed for functional and metabolic tolerance to alcohol using accelerating rotarod and blood EtOH concentrations, respectively. The remaining mice were assessed for tolerance to THC‐induced hypothermia, and whole‐brain CB1R expression was assessed in all mice. EtOH intake was on par with levels previously reported in adolescent mice. Edible THCwas well‐consumed, but consumption decreased at the highest dose provided. Locomotor activity increased following EtOH intake and decreased following edible THCconsumption, and edible THCincreased fluid intake in general. The use of alcohol produced neither functional nor metabolic tolerance to an alcohol challenge. However, the use of edible THCimpaired subsequent drug‐free rotarod performance and was associated with a reduction in THC's hypothermic effect. Adolescent mice self‐administered both alcohol and edible THCto a degree sufficient to acutely impact locomotor activity. However, only edible THCconsumption had lasting effects during short‐term abstinence. Thus, this adolescent co‐use model could be used to explore sex differences in self‐administration and the impact substance co‐use might have on other domains such as mood and cognition. A newly‐developed edible THCmodel was combined with a traditional model of binge‐like alcohol drinking to permit adolescent mice to self‐administer these substances in a co‐use fashion. Mice consumed both substances to a degree sufficient to impact behavior. Edible THCand alcohol had divergent effects on mouse activity levels, and THC, but not alcohol, was associated with motor impairment and tolerance during short‐term abstinence. This model should allow for further exploration of the effects of co‐use of THCand alcohol.