Cross-Generational THC Exposure Alters Heroin Reinforcement in Adult Male Offspring

Background: An emerging area of preclinical research has investigated whether drug use in parents prior to conception influences drug responsivity in their offspring. The present work sought to further characterize such effects with cannabis by examining whether a parental THC history modified locomotor sensitization to morphine and self-administration of heroin in adult progeny. Methods: Male and female Sprague Dawley rats were exposed to eight injections of 0 or 1.5 mg/kg THC during adolescence and bred with subjects from the same dose group. In Experiment 1, adult male and female offspring (F1-THC and F1-Veh) underwent locomotor sensitization procedures with morphine over five trials followed by a 5-day abstinence period and a final morphine challenge. In Experiment 2, subjects were trained to self-administer heroin and tested under a number of conditions (FR1, FRS, FR10, PR, dose response assessment, extinction, cue- + stress-induced reinstatement). Results: Germline THC exposure had no effect on morphine locomotor sensitization. However, F1-THC males displayed a reduced motivation to self-administer heroin relative to F1-Veh males. Conclusions: The present data indicate that parental THC exposure alters the reinforcing properties of heroin in a sex-specific manner. As such, mild to moderate cannabis use during adolescence may alter heroin abuse liability for males in the subsequent generation, but have limited effects on females.