PMID- 15705357
OWN - NLM
STAT- MEDLINE
DCOM- 20050509
LR  - 20221207
IS  - 0006-3223 (Print)
IS  - 0006-3223 (Linking)
VI  - 57
IP  - 4
DP  - 2005 Feb 15
TI  - Continuous but not intermittent olanzapine infusion induces vacuous chewing 
      movements in rats.
PG  - 406-11
AB  - 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.
FAU - Turrone, Peter
AU  - Turrone P
AD  - Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
FAU - Remington, Gary
AU  - Remington G
FAU - Kapur, Shitij
AU  - Kapur S
FAU - Nobrega, Jose N
AU  - Nobrega JN
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Biol Psychiatry
JT  - Biological psychiatry
JID - 0213264
RN  - 0 (Dopamine Antagonists)
RN  - 0 (Receptors, Dopamine D2)
RN  - 0 (Serotonin Uptake Inhibitors)
RN  - 10028-17-8 (Tritium)
RN  - 12794-10-4 (Benzodiazepines)
RN  - 430K3SOZ7G (Raclopride)
RN  - J6292F8L3D (Haloperidol)
RN  - N7U69T4SZR (Olanzapine)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Behavior, Animal
MH  - Benzodiazepines/*administration & dosage/adverse effects/blood
MH  - Disease Models, Animal
MH  - Dopamine Antagonists/administration & dosage
MH  - Drug Administration Routes
MH  - Dyskinesia, Drug-Induced/etiology/*physiopathology
MH  - Haloperidol/administration & dosage
MH  - *Infusion Pumps
MH  - Male
MH  - Mastication/*drug effects
MH  - Olanzapine
MH  - Raclopride/pharmacology
MH  - Radioligand Assay/methods
MH  - Random Allocation
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Dopamine D2/metabolism
MH  - Selective Serotonin Reuptake Inhibitors/*administration & dosage/adverse 
      effects/blood
MH  - Time Factors
MH  - Tritium/pharmacology
EDAT- 2005/02/12 09:00
MHDA- 2005/05/10 09:00
CRDT- 2005/02/12 09:00
PHST- 2004/02/27 00:00 [received]
PHST- 2004/08/10 00:00 [revised]
PHST- 2004/10/04 00:00 [revised]
PHST- 2004/10/18 00:00 [accepted]
PHST- 2005/02/12 09:00 [pubmed]
PHST- 2005/05/10 09:00 [medline]
PHST- 2005/02/12 09:00 [entrez]
AID - S0006-3223(04)01103-5 [pii]
AID - 10.1016/j.biopsych.2004.10.023 [doi]
PST - ppublish
SO  - Biol Psychiatry. 2005 Feb 15;57(4):406-11. doi: 10.1016/j.biopsych.2004.10.023.