Abstract | RATIONALE: Mice lacking metabotropic glutamate receptors 5 (mGluR5) exhibit reduced glutamatergic function and behavioral abnormalities, including deficits in prepulse inhibition (PPI) of the startle response that may be relevant to schizophrenia. Thus, these mice are an animal model that may be used for preclinical evaluation of potentially new classes of antipsychotic compounds. Recent clinical studies have suggested several compounds that modulate glutamatergic transmission through distinct mechanisms, such as potentiation of the N-methyl-D: -aspartate ( NMDA) receptor glycine site, activation of group II mGluR, and activation of glutamate- cysteine antiporters, as being efficacious in the treatment of schizophrenia. OBJECTIVES: RESULTS: CONCLUSIONS: These findings provide evidence that the interactions between mGluR5 and NMDA receptors are involved in the regulation of PPI and suggest that activation of glutamate receptors, other than group II receptors, by increased endogenous glutamate transmission, may ameliorate the behavioral abnormalities associated with mGluR5 deficiency.
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Authors | Hwei-Hsien Chen, Astrid Stoker, Athina Markou |
Journal | Psychopharmacology
(Psychopharmacology (Berl))
Vol. 209
Issue 4
Pg. 343-50
(May 2010)
ISSN: 1432-2072 [Electronic] Germany |
PMID | 20217053
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Amino Acid Transport System y+
- Amino Acids
- Bridged Bicyclo Compounds, Heterocyclic
- Excitatory Amino Acid Agonists
- Glycine Plasma Membrane Transport Proteins
- Grm5 protein, mouse
- LY 379268
- Receptor, Metabotropic Glutamate 5
- Receptors, Metabotropic Glutamate
- Receptors, N-Methyl-D-Aspartate
- Slc6a9 protein, mouse
- Slc7a11 protein, mouse
- Acetylcysteine
- Sarcosine
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Topics |
- Acetylcysteine
(pharmacology)
- Acoustic Stimulation
- Amino Acid Transport System y+
(agonists, metabolism)
- Amino Acids
(pharmacology)
- Analysis of Variance
- Animals
- Bridged Bicyclo Compounds, Heterocyclic
(pharmacology)
- Dose-Response Relationship, Drug
- Excitatory Amino Acid Agonists
(pharmacology)
- Female
- Glycine Plasma Membrane Transport Proteins
(antagonists & inhibitors, metabolism)
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Neural Inhibition
(drug effects)
- Receptor, Metabotropic Glutamate 5
- Receptors, Metabotropic Glutamate
(agonists, deficiency, genetics)
- Receptors, N-Methyl-D-Aspartate
(agonists, metabolism)
- Reflex, Startle
(drug effects)
- Sarcosine
(pharmacology)
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