COCAINE CROSS-SENSITIZATION TO DOPAMINE UPTAKE INHIBITORS - UNIQUE EFFECTS OF GBR12909

Repeated administration of cocaine will cross-sensitize the locomotor response to a variety of psychomotor stimulants. The ability of cocain e to cross-sensitize the locomotor effects of other psychomotor stimul ants provides information relevant to the pharmacological mechanisms u nderlying the sensitization process. The purpose of the current experi ment was to investigate the ability of cocaine to cross-sensitize the locomotor effects of several dopamine uptake blockers with unique phar macological profiles. Cocaine (40 mg/kg, IP) or saline was administere d prior to a locomotor session on day one. On day 2, a full dose-effec t curve was established for the locomotor effects of cocaine, RTI-55, mazindol, and GBR12909. Previous exposure to Cocaine significantly aff ected locomotor activity and stereotopy-like behavior produced by coca ine, mazindol, RTI-55, and GBR12909. However, GBR12909 was unique in t hat the maximal stimulant effect and slope of the dose-effect curve wa s significantly depressed and the stereotopy-like behavior was unchang ed. Thus, despite the similarity of these compounds in their ability t o inhibit dopamine uptake, cocaine-induced sensitization did not gener alize to GBR12909. This study further demonstrates the unique pharmaco logy of GBR12909 and supports the further study of this compound as a potential treatment medication for cocaine abuse.