Cocaine-induced behavioral sensitization: effects of haloperidol and SCH 23390 treatments

The objective of this study was to determine whether the development of behavioral sensitization to cocaine could be prevented by high doses of the dopamine receptor antagonists haloperidol and SCH 23390. In two experiments, male Wistar rats were injected daily for 4 days with either cocaine (15 mg/kg, IP) or vehicle in combination with haloperidol (1.0 mg/kg, IP), SCH 23390 (0.5 mg/kg, SC), or vehicle. After the daily injections, the rats were tested for locomotor activity in photocell arenas. At 24 h after the last preexposure test session, all rats were given a challenge injection of cocaine (15 mg/kg, IP) and tested for activity. Cocaine treatments produced a greater relative increase in locomotor activity with repeated exposure compared to vehicle treatments (i.e., sensitization). Moreover, the acute activating effects of cocaine over days were blocked by both haloperidol and SCH 23390. The coadministration of haloperidol, but not SCH 23390, blocked the development of behavioral sensitization to cocaine. That is, after the cocaine challenge injection, rats pretreated with SCH 23390 and cocaine did not differ from rats preexposed only to cocaine, whereas rats pretreated with haloperidol and cocaine did not differ from rats pretreated only with vehicle. Pretreatment with haloperidol or SCH 23390 without cocaine enhanced the locomotor-activating effects of the subsequent cocaine challenge injection. These findings suggest that cocaine-induced behavioral sensitization may develop as a result of repeated dopamine D1- or D2-type receptor stimulation, and that brief dopamine antagonist treatments enhance subsequent behavioral sensitivity to cocaine.