Apomorphine fails to inhibit cocaine-induced behavioral hypersensitivity.

The subchronic administration of cocaine will induce a behavioral sensitization to challenge doses of the drug administered several days after cessation of treatment. This sensitization is similar behaviorally to that observed for other stimulants such as amphetamine. Similarities and differences in the sensitization induced by cocaine and amphetamine (which are though to have different mechanisms of actions although common behavioral outcomes) have not been thoroughly studied. The purpose of the present experiment was to examine the effects of these two drugs on basic horizontal locomotion and changes occurring subsequent to their subchronic administration in mice. Cocaine and amphetamine were administered acutely in various doses to compare time and dose responses in the behavioral paradigm used (infrared detection of horizontal locomotion). Subsequently, cocaine (10 mg/kg) or amphetamine (2.5 mg/kg) were administered twice a day for 5 days and the animals challenged 3 days after the last treatment with the same doses received subchronically. Two other groups of mice received the same subchronic treatment and in addition were administered 80 micrograms/kg apomorphine (5 to 15 min after each dose of the stimulant) and then tested for their response to challenge doses of the stimulants 72 hours after the last pretreatment dose. Acutely, cocaine produced a maximum locomotor activity that was significantly lower than that of amphetamine and the former had a much shorter duration of action than the latter. After subchronic administration, both stimulants induced sensitization, however, apomorphine inhibited the sensitization induced by amphetamine but failed to do so in the cocaine-treated animals. Possible mechanisms for these differences are discussed.