Effects of Adolescent Δ9-Tetrahydrocannabinol Exposure on the Behavioral Effects of Cocaine in Adult Sprague-Dawley Rats

Cannabis is the most popular, illegal drug used by adolescents in the United States. Exposure to cannabis and its main psychoactive ingredient, Delta 9-tetrahydrocannabinol (THC), during adolescence may have long-lasting effects on the development of behavioral and neurobiological processes. This study investigated the effects of chronic adolescent exposure to THC on sensitization to the psychomotor-stimulating effects of cocaine and on the reinforcing effects of cocaine in adult male Sprague-Dawley rats. During adolescence (P28-P45), rats were given once-daily intraperitoneal injections of either vehicle or 1 mg/kg THC. On P90, the acute locomotor-stimulating effects of cocaine and sensitization to cocaine were evaluated. Also, cocaine-maintained behavior was evaluated by determining within-session cocaine dose-effect curves, acquisition of behavior maintained by a small cocaine dose (0.1 mg/kg/infusion), and breakpoints on a progressive ratio schedule of reinforcement. In general, there was no effect of adolescent THC exposure on the locomotor-stimulating effects of cocaine following acute or repeated administration. However, the reinforcing effects of cocaine were potentiated in rats treated with THC during adolescence, but this effect was only observed with small doses of cocaine. Rats exposed to THC during adolescence also more rapidly acquired self-administration behavior when a small cocaine dose was available. Together, these results demonstrate that exposure to THC during adolescence may enhance sensitivity to cocaine and/or enhance the reinforcing effects of cocaine even into adulthood under certain conditions. In conclusion, frequent exposure to THC during adolescence may produce long-lasting changes in behavior, possibly increasing susceptibility to addiction. Public Health Significance Repeated exposure to the active ingredient in cannabis during adolescence produces changes in behavior that persist into adulthood. These present data suggest that frequent use of cannabis during adolescence may enhance the reinforcing effects of cocaine, increasing susceptibility to addiction.