Pharmacological effects of acute and repeated administration of Delta(9)-tetrahydrocannabinol in adolescent and adult rats.

Adolescents of many mammalian species exhibit rapid physiological change that is accompanied by behaviors such as increased risk taking and social interaction with peers. Marijuana abusers frequently report that their initial use occurred during adolescence. Our goal was to determine whether the in vivo effects of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) differed in adolescent and adult rats. Following initial testing with Delta(9)-THC in adolescent [postnatal day (PN)29] and adult (>PN60) rats of both sexes, we injected rats twice daily with 10 mg/kg Delta(9)-THC or vehicle for 9.5 days. Subsequently, rats were again injected with their initial dose of Delta(9)-THC and tested. In all rats, Delta(9)-THC produced dose-dependent locomotor suppression, antinociception, hypothermia and catalepsy. Some age-dependent differences in potency and efficacy were noted. Although Delta(9)-THC dose-effect functions were more similar across age after repeated exposure, subchronic dosing produced greater change in the hypothermic and locomotor effects of Delta(9)-THC in adolescents, but less change in its antinociceptive effects. These results suggest that the effects of initial exposure to Delta(9)-THC may not be entirely predictive of the effects of repeated exposure. Despite similarities in pharmacological effects of Delta(9)-THC after repeated use, adolescents and adults may exhibit differences in the pattern of transition from use to abuse.