We examined the effects of
JP-1302 (a selective alpha2C antagonist),
BRL-44408 (a selective alpha2A antagonist) and
yohimbine (a non-selective alpha2 antagonist) on
haloperidol-induced
bradykinesia and
catalepsy in mice to elucidate the role of alpha2
adrenoceptor subtypes in modifying extrapyramidal
motor disorders.
JP-1302 (0.1-1 mg/kg, s.c.) dose-dependently ameliorated
haloperidol-induced
bradykinesia in the pole-test and reversed the
catalepsy time increased by
haloperidol. Antibradykinetic and anticataleptic actions of
JP-1302 were statistically significant at 0.3 and 1 mg/kg, and these doses did not alter the ambulatory distance, rearing or center-perimeter residence time in the open-field test.
BRL-44408 (1-10 mg/kg, s.c.) and
yohimbine (0.3-3 mg/kg, i.p.) also ameliorated
haloperidol-induced
bradykinesia and
catalepsy. However, both agents significantly decreased ambulatory distance and rearing in the open-field test, possibly reflecting their anxiogenic actions associated with alpha2A antagonism. The present study shows for the first time that blockade of alpha2C receptors can alleviate
antipsychotic-induced extrapyramidal
motor disorders without affecting gross behaviors.