Assessment of Acute Motor Effects and Tolerance Following Self-Administration of Alcohol and Edible THC in Adolescent Male Mice.

Abstract

BACKGROUND\nCannabinoids 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.\n\n\nMETHODS\nAdolescent male C57BL/6J mice had daily, limited access to one of two edible doughs (THC or control), to one of two fluids (ethanol or water), and in one of two orders (dough-fluid or fluid-dough). Home cage locomotor activity was recorded both during 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 ethanol concentrations, respectively. The remaining mice were assessed for tolerance to THC-induced hypothermia, and whole-brain CB1R expression was assessed in all mice.\n\n\nRESULTS\nEthanol intake was on par with levels previously reported in adolescent mice. Edible THC was well-consumed, but consumption decreased at the highest dose provided. Locomotor activity increased following ethanol intake and decreased following edible THC consumption, and edible THC increased fluid intake in general. Use of alcohol produced neither functional nor metabolic tolerance to an alcohol challenge. However, use of edible THC impaired subsequent drug-free rotarod performance and was associated with a reduction in THC s hypothermic effect.\n\n\nCONCLUSIONS\nAdolescent mice self-administered both alcohol and edible THC to a degree sufficient to acutely impact locomotor activity. However, only edible THC consumption had lasting effects during short-term abstinence. Thus, this adolescent co-use model could be used to explore sex differences in self-administration as well as the impact substance co-use might have on other domains such as mood and cognition.