1

Marijuana is the most popular illegal drug used in America among adolescents. Exposure to marijuana's main psychoactive ingredient Δ9-tetrahydrocannabinol (THC) during adolescence may have enduring effects on behavior during adulthood. This study investigated the effects of chronic adolescent exposure to THC on the reinforcing effects of cocaine and sensitization to the psychomotor stimulating effects of cocaine in male Sprague-Dawley rats. During adolescence (P28-45), rats were given once daily i.p. injections of either vehicle or 1 mg/kg THC. On P90 when considered full adults, we analyzed cocaine self-administration behavior by evaluating (1) within-session cocaine dose-effect curves, (2) acquisition of a small dose of cocaine (0.1 mg/kg/inj), (3) breakpoints on a progressive ratio schedule of reinforcement, and (4) locomotor activity sensitization to cocaine. Rats treated with THC during adolescence showed potentiation of the reinforcing effects of small doses of cocaine and were more likely to acquire self-administration with access to small cocaine doses. However, the breakpoint or motivation for cocaine was unchanged between the two treatment groups under the progressive ratio testing. There was no difference in locomotor sensitization to cocaine, but rats treated with THC during adolescence showed an overall increased response to the psychomotor stimulating effects of cocaine. Together, these results demonstrate that exposure to THC during adolescence alters the reinforcing and psychomotor stimulating effects of cocaine, suggesting that adolescent THC exposure produces long-lasting changes in the brain, specifically in reward systems.