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) receptor antagonists. Yet, long-term DA antagonist administration enhances neuronal responsiveness to DA in several pathways, including the mesolimbic system. This study compared the effects of short-term versus long-term administration of the DA antagonist, haloperidol, on cocaine place conditioning. In the short-term study, rats were maintained on haloperidol or vehicle for the 10 days of place conditioning. Place conditioning to moderate doses of cocaine (10-15 mg/kg) was attenuated significantly, consistent with the dopaminergic actions of haloperidol and cocaine. In the second study, rats were administered haloperidol after place conditioning which had no effect on the expression of this behavior. Finally, rats were maintained on haloperidol for 30 days prior to and throughout place conditioning and testing which resulted in significant place conditioning at low cocaine doses (2.5-7.5 mg/kg). Because these cocaine doses do not support place conditioning in vehicle-maintained rats, these data suggest that long-term haloperidol administration enhances the sensitivity to these behavioral effects in contrast to the attenuation seen with short-term haloperidol administration. These results have wide-ranging implications for cocaine abuse treatment, particularly among schizophrenic populations.