LONG-TERM HALOPERIDOL ADMINISTRATION ENHANCES AND SHORT-TERM ADMINISTRATION ATTENUATES THE BEHAVIORAL-EFFECTS OF COCAINE IN A PLACE CONDITIONING PROCEDURE

Many behavioral effects of cocaine are attenuated by dopamine (DA) rec eptor antagonists. Yet, long-term DA antagonist administration enhance s neuronal responsiveness to DA in several pathways, including the mes olimbic system. This study compared the effects of short-term versus l ong-term administration of the DA antagonist, haloperidol, on cocaine place conditioning. In the short-term study, rats were maintained on h aloperidol or vehicle for the 10 days of place conditioning. Place con ditioning to moderate doses of cocaine (10-15 mg/kg) was attenuated si gnificantly, consistent with the dopaminergic actions of haloperidol a nd cocaine. In the second study, rats were administered haloperidol af ter place conditioning which had no effect on the expression of this b ehavior. Finally, rats were maintained on haloperidol for 30 days prio r to and throughout place conditioning and testing which resulted in s ignificant place conditioning at low cocaine doses (2.5-7.5 mg/kg). Be cause these cocaine doses do not support place conditioning in vehicle -maintained rats, these data suggest that long-term haloperidol admini stration enhances the sensitivity to these behavioral effects in contr ast to the attenuation seen with short-term haloperidol administration . These results have wide-ranging implications for cocaine abuse treat ment, particularly among schizophrenic populations.