EVIDENCE FOR AN INVOLVEMENT OF MUSCARINIC CHOLINERGIC SYSTEMS IN THE INDUCTION BUT NOT EXPRESSION OF BEHAVIORAL SENSITIZATION TO COCAINE

The present study was designed to determine whether the muscarinic cho linergic antagonist scopolamine can prevent the expression and inducti on of sensitization to the locomotor-activating effects of cocaine. Ra ts received one daily injection of cocaine (20 mg/kg i.p.) for 5 days. Two days after withdrawal of pretreatment, rats were pretreated with scopolamine (3.0 mg/kg s.c) or its vehicle and challenged 15 min later with either saline or cocaine (20-30 mg/kg i.p.). In a second set of experiments, scopolamine (3.0 mg/kg s.c) or its vehicle was given in c ombination with either saline or cocaine (20 mg/kg i.p.) for 5 days. A ctivity in response to saline and to cocaine (20 mg/kg i.p.) was asses sed on day 7. The effects of acute administration of scopolamine (3.0 mg/kg s.c.) on cocaine-induced locomotor activity were also assessed. Acute administration of scopolamine increased both distance traveled a nd time spent in stereotypy. When scopolamine was administered 15 min prior to an acute injection of cocaine, a significant increase in the behavioral response to cocaine was seen. Daily injections of cocaine f or 5 days produced sensitized behavioral responses to a subsequent coc aine challenge. Acute administration of scopolamine to animals preexpo sed and sensitized to cocaine did not disrupt the expression of sensit ization to the locomotor and stereotypic effects of cocaine. In contra st, when scopolamine was given in combination with cocaine for 5 days, sensitization to the locomotor-activating effects of cocaine was prev ented. These results suggest an important role of cholinergic muscarin ic systems in mediating sensitization to the locomotor-activating effe cts of cocaine, which occurred after the repeated context-independent administration of this agent. In contrast, the enhanced stereotypic ef fects in response to the repeated administration of cocaine seem to be independent of alterations in muscarinic cholinergic transmission. (C ) 1996 Wiley-Liss, Inc.