Pretreatment with Δ9-tetrahydrocannabinol (THC) increases cocaine-stimulated activity in adolescent but not adult male rats

Marijuana (Cannabis sativa) remains one of the most widely used illegal drugs, with adolescents being particularly vulnerable to its use and abuse. In spite of this, most studies are conducted in adult animals even though the effects might be quite different in adolescents. Additionally, the use of marijuana often precedes the use of other psychoactive drugs including cocaine, especially when marijuana exposure begins during early adolescence. The purpose of this study was to examine the effects of repeated Δ9- tetrahydrocannabinol (THC), the major active ingredient in marijuana, in adolescents compared to adults and to determine its subsequent effects on cocaine-stimulated activity. To this end, adolescent (postnatal day PND 34) and adult (PND 66) rats were administered 3 mg/kg/day THC for 8 days and locomotor activity was measured on days 1, 2, 7 and 8 after dosing. On day 12 (4 days after the last dose of THC), rats were injected with escalating doses of cocaine and behavior was recorded. Results show that THC depressed locomotor activity in adult rats but not in adolescents. However, following a cocaine challenge, adolescents exposed to THC showed increased locomotor responses to cocaine compared to chronic vehicle-injected controls. This was not seen in adults. These results show that the effects of cocaine are enhanced after THC in adolescents, but not adults, and that this might account for the greater transition to cocaine after early, as opposed to later, marijuana use.