Sex Differences in Response-Contingent Cannabis Vapor Administration During Adolescence Mediate Enduring Effects on Behavioral Flexibility and Prefrontal Microglia Activation in Rats
Cannabis and Cannabinoid Research January 8, 2024 Timothy G. Freels, S. Westbrook, E. Zamberletti et al.
Adolescent female rats self-administered more vaporized THC-dominant cannabis extract than adolescent males. In adulthood, only females exposed to cannabis during adolescence showed impairments in behavioral flexibility, requiring more trials and making more regressive errors on an attentional set-shifting task, compared to vehicle-exposed rats. These sex differences were not observed when rats received a noncontingent dosing regimen that matched the amount females self-administered. No differences were found in effort-based decision making. In the medial prefrontal cortex, only female cannabis-exposed rats had more reactive microglia, with no changes in myelin basic protein or dendritic spine density. The findings indicate sex-specific long-term effects of adolescent cannabis use on brain structure and behavior.