Preferential inhibition of dizocilpine-induced hyperlocomotion by olanzapine

This study examined the putative inhibitory effect of the atypical antipsyc hotic, olanzapine, on dizocilpine (MK-801)-induced stereotypy and hyperloco motion. Dizocilpine (0.1, 0.25 and 0.5 mg/kg) produced a dose-dependent inc rease in both stereotypy and hyperlocomotion. Pretreatment with olanzapine (0.25 and 0.5 mg/kg) inhibited the dizocilpine (0.5 mg/kg)-induced hyperloc omotion but not the stereotypy. At the higher doses (1, 2 and 4 mg/kg), ola nzapine blocked both the stereotypy and hyperlocomotion induced by dizocilp ine. Similarly, olanzapine, 0.25 and 0.5 mg/kg, did not inhibit apomorphine (3 mg/kg)-induced stereotypy, whereas the higher dose (1 mg/kg) blocked it . We also studied the effect of olanzapine on spontaneous locomotor activit y and catalepsy. Olanzapine (0.25 and 0.5 mg/kg) did not induce a decrease in spontaneous locomotor activity but did so at the higher doses (1, 2 and 4 mg/kg). The lower doses (0.25, 0.5 and 1 mg/kg) did not induce catalepsy but higher doses (2 and 4 mg/kg) induced a significant catalepsy which last ed for more than 4 h. The results thus showed that, at lower doses, olanzap ine selectively inhibited behaviours mediated by the mesolimbic/mesocortica l system while at higher doses it inhibited behaviours mediated by both mes olimbic/mesocortical and nigrostriatal systems. Therefore, the minimal extr apyramidal side-effects produced by olanzapine at effective doses might be due to its preferential action at the mesolimbic/mesocortical area. (C) 199 9 Elsevier Science B.V. All rights reserved.