Differential tolerance to cataleptic effects of SCH 23390 and haloperidol after repeated administration

The development of tolerance to the cataleptic effect of the selective D-1 antagonist SCH 23390 (0.5 mg/kg/day SC or 0.1 mg/kg/day SC) and haloperidol (1 mg/kg/day SC) during repeated administration was investigated. Catalepsy in rats was measured using the horizontal bar method. SCH 23390 induced a dose-related cataleptic effect of short duration, whereas the cataleptic effect of haloperidol appeared more slowly and lasted longer. Marked tolerance to the cataleptic effect of haloperidol developed already 6 days from the beginning of the treatment. The cataleptic effect of the higher dose regimen of SCH 23390 was also significantly reduced after 6 days' treatment. However, unlike haloperidol, this subacute tolerance was gradually reversed and was no longer significant after 12 and 18 days. The cataleptic response to the lower dose of SCH 23390 (0.1 mg/kg/day) was not significantly altered during the treatment and no initial catalepsy tolerance was observed with this dose regimen. These results suggest that different mechanisms are involved in the expression of cataleptic behaviour during chronic treatment with SCH 23390 and classical antipsychotics, such as haloperidol.