A Characterization of Cross-generational THC Exposure and Offspring Responsivity to Cocaine, Nicotine and Opiates

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 and self-administration of cocaine (Experiment 1), nicotine (Experiment 2) and opiates (Experiment 3) in adult progeny. Adolescent male and female Sprague Dawley rats were administered 1.5 mg/kg THC or vehicle every 3rd day during PND 28-49. On PND 65, males and females within the same dose group were bred together and the resultant pups cross fostered to control dams. In Experiment 1A, a baseline activity monitoring session was run followed by 7 days of cocaine injections during which subjects (male) from these breeding pairs were placed in activity chambers. After a 7-day washout period, a challenge dose of cocaine was administered and subjects were again monitored. In Experiment 1B, F1 subjects were implanted with a jugular catheter and underwent cocaine self-administration (FR1, FR5, FR10, PR, dose response assessment, extinction, cue- + stress-induced reinstatement). Cocaine induced a significant increase in behavioral sensitization and maintained responding across the various reinforcement schedules. There was no consistent effect of parental THC exposure on any endpoint assessed. In Experiments 2 and 3, similar locomotor sensitization and IVSA parameters were utilized (using male and females). Locomotor sensitization with nicotine and morphine was unaffected by germline THC exposure. While nicotine self-administration was only marginally affected, F1-THC males displayed a reduced motivation to self-administer heroin compared to F1-Veh males. The present data indicate that parental THC exposure alters the reinforcing properties of abused drugs in a drug- and 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 cocaine and nicotine.