Sex difference in the development of hypersensitivity or tolerance to haloperidol in the rat

Sex difference in the cataleptic response to continuous or intermittent administration of haloperidol (1 mg/kg, i.p.) was examined in the rat. Weekly administration of haloperidol induced a hypersensitivity to haloperidol itself to a greater extent in adult female rats as compared to adult males. Five daily injection of haloperidol induced a marked tolerance to haloperidol in adult female rats but not in males. Ovariectomy in adult rats failed to alter the development of hypersensitivity or tolerance to haloperidol. Orchiectomy in adult rats resulted in the development of a hypersensitivity to haloperidol during the weekly administration and a tolerance during daily injection of haloperidol. In immature female rats, weekly administration began at 3 weeks of age induced a marked increase in the intensity of haloperidol-induced catalepsy at 7 weeks of age. Daily injection of haloperidol in 3-week-old rats did not show any significant sex difference. These findings suggest that exposure to sex hormones probably during the time of puberty onset, results in a modification of the activity of dopaminergic and/or related neurons responsible for cataleptic behavior to female and male types. Female sex hormones appear to induce a persistent modification of the dopaminergic system at a certain critical period during the maturation.