Document Detail


Effect of antipsychotic treatment on the prepulse inhibition deficit of mGluR5 knockout mice.
MedLine Citation:
PMID:  14615875     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
RATIONALE: Prepulse inhibition of the startle response (PPI), a model of sensorimotor gating, is deficient in persons with schizophrenia. In rodents, the reversal of induced deficits in PPI demonstrates predictive validity for identifying antipsychotic treatments. Metabotropic glutamate receptor 5 (mGluR5) has been implicated in schizophrenia, in part because mGluR5 knockout (KO) mice exhibit PPI deficits. OBJECTIVE: We examined whether mGluR5 KO mice might serve as a novel model for detecting antipsychotic treatments. METHODS: Using C57BL/6J or 129SvPasIco mice, we first determined doses of the typical antipsychotic raclopride or the atypical antipsychotic clozapine that were effective in blocking the PPI-disruptive effects of amphetamine or ketamine, respectively. We then examined the effects of these doses on the deficit in PPI in mGluR5 KO mice. RESULTS: Administration of raclopride or clozapine reversed either an amphetamine or a ketamine-induced PPI deficit, as had the novel mood stabilizer lamotrigine in previous studies. In contrast, the PPI deficit of the mGluR5 KO mice was not altered by administration of raclopride, clozapine, or lamotrigine. The serotonin(2A) antagonist M100,907 was also ineffective in reversing the mGluR5 KO deficit in PPI. CONCLUSIONS: Most of the compounds examined ameliorated at least a subset of pharmacologically induced PPI deficits. That none of the antipsychotic treatments attenuated the PPI deficit in the mGluR5 KO mice indicates that this model is not predictive of known treatments for schizophrenia, but does not preclude a role for the mGluR5 receptor in schizophrenia or other psychiatric disorders.
Authors:
S A Brody; F Conquet; M A Geyer
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.     Date:  2003-11-13
Journal Detail:
Title:  Psychopharmacology     Volume:  172     ISSN:  0033-3158     ISO Abbreviation:  Psychopharmacology (Berl.)     Publication Date:  2004 Mar 
Date Detail:
Created Date:  2004-03-01     Completed Date:  2004-06-28     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7608025     Medline TA:  Psychopharmacology (Berl)     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  187-95     Citation Subset:  IM    
Affiliation:
Departments of Psychiatry and Neurosciences, University of California San Diego, 9500 Gilman Drive, CA 92093-0804, La Jolla, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antipsychotic Agents / pharmacology*
Female
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Neural Inhibition / drug effects*,  physiology
Receptors, Metabotropic Glutamate / deficiency*,  genetics
Startle Reaction / drug effects*,  physiology
Grant Support
ID/Acronym/Agency:
F31MH12961/MH/NIMH NIH HHS; R01DA02925/DA/NIDA NIH HHS; R37MH42228/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/Antipsychotic Agents; 0/Receptors, Metabotropic Glutamate; 0/metabotropic glutamate receptor 5

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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