Preferential inhibition of dizocilpine-induced hyperlocomotion by olanzapine

Eur J Pharmacol. 1999 Feb 26;368(1):1-7. doi: 10.1016/s0014-2999(98)00982-0.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / pharmacology*
  • Antipsychotic Agents / therapeutic use
  • Apomorphine / pharmacology
  • Benzodiazepines
  • Catalepsy / chemically induced
  • Dizocilpine Maleate / pharmacology*
  • Dopamine Agonists / pharmacology
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Locomotion / drug effects*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Motor Activity / drug effects
  • Olanzapine
  • Pirenzepine / adverse effects
  • Pirenzepine / analogs & derivatives*
  • Pirenzepine / pharmacology
  • Pirenzepine / therapeutic use
  • Stereotyped Behavior / drug effects
  • Stereotypic Movement Disorder / drug therapy

Substances

  • Antipsychotic Agents
  • Dopamine Agonists
  • Excitatory Amino Acid Antagonists
  • Benzodiazepines
  • Pirenzepine
  • Dizocilpine Maleate
  • Apomorphine
  • Olanzapine