COCAINE-INDUCED BEHAVIORAL SENSITIZATION - EFFECTS OF HALOPERIDOL ANDSCH-23390 TREATMENTS

The objective of this study was to determine whether the development o f behavioral sensitization to cocaine could be prevented by high doses of the dopamine receptor antagonists haloperidol and SCH 23390. In tw o experiments, male Wistar rats were injected daily for 4 days with ei ther 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 dai ly injections, the rats were tested for locomotor activity in photocel l arenas. At 24 h after the last preexposure test session, all rats we re given a challenge injection of cocaine (15 mg/kg, IP) and tested fo r activity. Cocaine treatments produced a greater relative increase in locomotor activity with repeated exposure compared to vehicle treatme nts (i.e., sensitization). Moreover, the acute activating effects of c ocaine over days were blocked by both haloperidol and SCH 23390. The c oadministration of haloperidol, but not SCH 23390, blocked the develop ment of behavioral sensitization to cocaine. That is, after the cocain e challenge injection, rats pretreated with SCH 23390 and cocaine did not differ from rats preexposed only to cocaine, whereas rats pretreat ed with haloperidol and cocaine did not differ from rats pretreated on ly with vehicle. Pretreatment with haloperidol or SCH 23390 without co caine enhanced the locomotor-activating effects of the subsequent coca ine challenge injection. These findings suggest that cocaine-induced b ehavioral sensitization may develop as a result of repeated dopamine D -1- or D-2-type receptor stimulation, and that brief dopamine antagoni st treatments enhance subsequent behavioral sensitivity to cocaine.