Continuous but not intermittent olanzapine infusion induces vacuous chewing movements in rats

Biol Psychiatry. 2005 Feb 15;57(4):406-11. doi: 10.1016/j.biopsych.2004.10.023.

Abstract

Background: Continuous, but not intermittent, infusion with a conventional antipsychotic (haloperidol, HAL) can induce the vacuous chewing movement (VCM) syndrome in rats. The objective of this study was to determine whether continuous, versus intermittent, olanzapine (OLZ) infusion differently affects the development of VCMs.

Methods: Experiment 1: Animals were treated with 7.5 mg/kg/day of OLZ or vehicle (VEH) via either minipump (MP) or daily subcutaneous (SC) injections for 8 weeks. Experiment 2: A separate group of rats were treated with 15 mg/kg/day of OLZ, or 1 mg/kg/day of HAL or VEH via MP for 8 weeks. Dopamine D2 receptor occupancy levels were measured, ex vivo, with [3H]-raclopride.

Results: Experiment 1: Rats receiving 7.5 mg/kg/day of OLZ via MP (51% D2 occupancy), but not those receiving the same dose via daily SC injections (94% peak D2 occupancy), showed significant VCM levels compared with control animals (p = .02). Experiment 2: Both OLZ (67% D2 occupancy) and HAL (79% D2 occupancy) led to similar increases in VCMs compared with VEH (p = .005).

Conclusions: This study provides strong evidence that even an atypical antipsychotic like OLZ, which rarely gives rise to tardive dyskinesia in the clinic, can lead to the VCM syndrome in rats if the antipsychotic is administered in a method (via MP) that leads to continuous presence of the drug in the brain.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Behavior, Animal
  • Benzodiazepines / administration & dosage*
  • Benzodiazepines / adverse effects
  • Benzodiazepines / blood
  • Disease Models, Animal
  • Dopamine Antagonists / administration & dosage
  • Drug Administration Routes
  • Dyskinesia, Drug-Induced / etiology
  • Dyskinesia, Drug-Induced / physiopathology*
  • Haloperidol / administration & dosage
  • Infusion Pumps*
  • Male
  • Mastication / drug effects*
  • Olanzapine
  • Raclopride / pharmacology
  • Radioligand Assay / methods
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D2 / metabolism
  • Serotonin Uptake Inhibitors / administration & dosage*
  • Serotonin Uptake Inhibitors / adverse effects
  • Serotonin Uptake Inhibitors / blood
  • Time Factors
  • Tritium / pharmacology

Substances

  • Dopamine Antagonists
  • Receptors, Dopamine D2
  • Serotonin Uptake Inhibitors
  • Tritium
  • Benzodiazepines
  • Raclopride
  • Haloperidol
  • Olanzapine