Behavioral sensitization to amphetamine follows chronic administration of the CB1 agonist WIN 55,212-2 in Lewis rats

The extent to which acute and repeated administration of the CB1 agonist WIN 55,212-2 would affect the stimulatory properties of amphetamine was assessed in Lewis rats. In the first experiment, Lewis rats were treated with either 1 mg/kg of WIN 55,212-2 or vehicle and subsequently treated with 2 mg/kg amphetamine. Acute treatment with WIN 55,212-2 initially increased locomotor activity and then attenuated the stimulating effect of amphetamine on locomotion and exploration (as measured by rears). In a separate experiment, Lewis rats were given daily injections of either WIN 55,212-2 (1 mg/kg) or vehicle for 10 days and the effects of amphetamine were assessed at 1 and 3 days following the last chronic cannabinoid treatment. Those rats, which had been treated with WIN 55,212-2. had an enhanced response to amphetamine with rearing but not with ambulatory movements, suggesting the occurrence of behavioral cross-sensitization to the ability of amphetamine to increase rearing. These data add to the growing evidence that there is at least some overlap between those neural systems acted upon by cannabinoids and those that are believed to be involved in incentive properties associated with other drugs of abuse. (C) 2002 Elsevier Science Inc. All rights reserved.