Tolerance of haloperidol catalepsy.

Haloperidol (0.75 and 1.5 mg/kg p.o.) was administered daily for 16 days to male Wistar rats. The animals received an acute injection of haloperidol (0.5-2.0 mg/kg i.p. or 1.0-4.0 mg/kg p.o.) and catalepsy was measured. After 16 days on haloperidol, all animals became tolerant to the drug, exhibiting decreased cataleptic response to haloperidol; the intensity of catalepsy returned to normal after an additional 16 days abstinence from the drug. In addition, a group of animals treated and tested daily for catalepsy demonstrated that the time course of tolerance development to haloperidol was biphasic, with a rapid phase (T1/2 = 2.5 days) and a slower phase (T1/2 = 5.5 days).