Cross-generational THC Exposure Weakly Attenuates Cocaine's Rewarding Effects in Adult Male Offspring.

Adolescents represent a large demographic of marijuana consumers. Regrettably, use during this developmental period has been associated with above average health risks. A growing body of evidence suggests that adolescent drug use in the lifetime of a parent can modify behavior and neurochemistry in descendants without direct exposure. The current study was designed to evaluate the effects of pre-conception THC during adolescence on vulnerability to cocaine in adult male offspring. Male and female rats were given an intermittent THC (0 or 1.5 mg/kg) exposure regimen during the adolescent window and mated with drug group conspecifics in adulthood. F1-THC and F1-Veh pups were cross fostered to drug naïve control dams. In Experiment 1, adult offspring underwent cocaine (0 or 15 mg/kg) locomotor sensitization procedures and showed no effect of parental THC exposure on locomotor activity. In Experiment 2, intravenous catheters were implanted and subjects were tested under a number of reinforcement schedules with cocaine (FR1, FR5, FR10, PR, dose-response, extinction, cue + stress induced reinstatement). F1-THC subjects exhibited a slight decrease in cocaine responding during acquisition and a more rapid extinction, but they failed to produce significant differences on any other measure. These findings indicate that adolescent cannabis use likely has minimal effects on cocaine abuse liability in the next generation.

Pre-conception exposure to THC fails to impact nicotine reward in adult offspring.

Exposure to environmental stimuli in one generation can produce altered behavioral and neurobiological phenotypes in descendants. Recent work has shown that parental exposure to cannabinoids alters the rewarding properties of other abused drugs in the subsequent generation. However, whether preconception Δ9-tetrahydrocannabinol (THC) administration modifies the affective properties of nicotine in offspring is unknown. To address this question, male and female rats (F0) received THC (0 or 1.5 mg/kg) throughout the adolescent window and were bred on PND 65. In Experiment 1, adult F1-THC and F1-Veh progeny (males and females) underwent nicotine locomotor sensitization procedures during which nicotine (0 or 0.4 mg/kg) was administered every other day for five exposures, and locomotor activity was recorded on each exposure followed by a final nicotine challenge. There was no cross-generational effect of THC on nicotine locomotor sensitization, although acute exposure to nicotine produced greater activity in females relative to males independent of THC history. In Experiment 2, adult F1-THC and F1-Veh progeny (males and females) were implanted with jugular catheters and trained to self-administer nicotine (0.03 mg/kg/infusion). Following acquisition, all subjects were allowed to self-administer nicotine on a number of reinforcement schedules, e.g., FR2, FR5 and PR, followed by dose response and extinction procedures. Across all indices, F1-THC and F1-Veh subjects displayed similar IVSA of nicotine with no sex differences. The fact that there was no evidence of cross-generational effects of THC on nicotine suggests that such effects are drug-specific.

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, FR5, 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.