Continuous but not intermittent olanzapine infusion induces vacuous chewing movements in rats.
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.
Turrone
Peter
P
Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
Remington
Gary
G
Kapur
Shitij
S
Nobrega
José N
JN
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D001569:Benzodiazepines / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D004195:Disease Models, Animal; D018492:Dopamine Antagonists / Q000008:administration & dosage; D004333:Drug Administration Routes; D004409:Dyskinesia, Drug-Induced / Q000209:etiology / Q000503:physiopathology*; D006220:Haloperidol / Q000008:administration & dosage; D007260:Infusion Pumps; D008297:Male; D008409:Mastication / Q000187:drug effects*; D000077152:Olanzapine; D020891:Raclopride / Q000494:pharmacology; D011869:Radioligand Assay / Q000379:methods; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D013997:Time Factors; D014316:Tritium / Q000494:pharmacology
D001569:Benzodiazepines; D018492:Dopamine Antagonists; D006220:Haloperidol; D000077152:Olanzapine; D020891:Raclopride; D017448:Receptors, Dopamine D2; D017367:Selective Serotonin Reuptake Inhibitors; D014316:Tritium