Dose-catalepsy response to haloperidol in rat: effects of strain and sex

Haloperidol induced catalepsy with a continuous dose-response between 0 or 0.03 and 10 mg/kg, IP in Brown Norway (BN), Fischer (FR). Long-Evans (LE), and Sprague-Dawley (SD) rats, with similar ED50 values for males (0.23-0.42 mg/kg), and generally greater but more varied drug sensitivity in females (ED50 = 0.13-0.45 mg/kg). Inconsistent findings regarding a biphasic dose-effect relationship in SD male and LE female rats led to testing both sexes and strains up to 200 mg/kg. Females showed a greater tendency than males of both strains to yield lower catalepsy scores at doses greater than 10 mg/kg, but in association with gross neurological toxicity. This paradigm evidently is not an adequate model for a proposed biphasic relationship between doses of high potency neuroleptic agents and acute dystonia in man.