Preferential inhibition of dizocilpine-induced hyperlocomotion by olanzapine.
This study examined the putative inhibitory effect of the atypical antipsychotic, olanzapine, on dizocilpine (MK-801)-induced stereotypy and hyperlocomotion. Dizocilpine (0.1, 0.25 and 0.5 mg/kg) produced a dose-dependent increase in both stereotypy and hyperlocomotion. Pretreatment with olanzapine (0.25 and 0.5 mg/kg) inhibited the dizocilpine (0.5 mg/kg)-induced hyperlocomotion but not the stereotypy. At the higher doses (1, 2 and 4 mg/kg), olanzapine blocked both the stereotypy and hyperlocomotion induced by dizocilpine. 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 activity 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 lasted for more than 4 h. The results thus showed that, at lower doses, olanzapine selectively inhibited behaviours mediated by the mesolimbic/mesocortical system while at higher doses it inhibited behaviours mediated by both mesolimbic/mesocortical and nigrostriatal systems. Therefore, the minimal extrapyramidal side-effects produced by olanzapine at effective doses might be due to its preferential action at the mesolimbic/mesocortical area.
Ninan
I
I
University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Kulkarni
S K
SK
D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D001058:Apomorphine / Q000494:pharmacology; D001569:Benzodiazepines; D002375:Catalepsy / Q000139:chemically induced; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009043:Motor Activity / Q000187:drug effects; D000077152:Olanzapine; D010890:Pirenzepine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D013239:Stereotyped Behavior / Q000187:drug effects; D019956:Stereotypic Movement Disorder / Q000188:drug therapy
D014150:Antipsychotic Agents; D018491:Dopamine Agonists; D018691:Excitatory Amino Acid Antagonists; D001569:Benzodiazepines; D010890:Pirenzepine; D016291:Dizocilpine Maleate; D001058:Apomorphine; D000077152:Olanzapine