Evaluation of age and sex differences in locomotion and catalepsy during repeated administration of haloperidol and clozapine in adolescent and adult rats

Adolescence is associated with characteristic behavioral patterns as well as with substantial neuronal pruning and re-organization of the brain. Recent research has determined that the effects of various centrally active drugs differ in adolescents and adults. This study examined the motor effects of two prototypic antipsychotics in adult [>postnatal day 70 (PN70)] and adolescent (PN30–PN39) rats. Rats were injected daily with saline, 0.3 mg/kg haloperidol, or 10 mg/kg clozapine for 10 days and activity and catalepsy were measured. Adolescents of both sexes were less sensitive to the cataleptic effects of haloperidol than were adults. Male adolescents were also less sensitive to the cataleptic effects of clozapine, although this difference was transitory. In contrast, female adults showed decreased sensitivity to clozapine's effects, differing from all other groups. These results suggest that adolescents of both sexes may be less sensitive to the extrapyramidal motor effects of haloperidol. Translational implications of the clozapine results are less clear; however, results suggest that developmental differences in neurochemical systems affected by clozapine that are also related to motor behavior may play a role. These results also emphasize the importance of age and sex as determinants of the pharmacological effects of these antipsychotics.