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Glutamate receptor mGlu2 and mGlu3 knockout striata are dopamine supersensitive, with elevated $D2^{High}$ receptors and marked supersensitivity to the dopamine agonist (+)PHNO

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Glutamate receptor mGlu2 and mGlu3 knockout striata are dopamine supersensitive, with elevated $D2^{High}$ receptors and marked supersensitivity to the dopamine agonist (+)PHNO

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Seeman, Philip Battaglia, Giuseppe Corti, Corrado Corsi, Mauro Bruno, Valeria
Description	Country affiliation: Canada Author Affiliation: Seeman P ( Department of Pharmacology, Medical Science Building, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada. philip.seeman@utoronto.ca)
Abstract	The finding that the mGlu2/3 metabotropic glutamate receptor agonist, LY404039, improves clinical symptoms in schizophrenia warrants a search for a possible interaction between mGlu2/3 receptors and dopamine D2 receptors. Here, this topic is examined in striatal tissue of mice lacking either mGlu2 or mGlu3 receptor. Such mice are known to be behaviorally supersensitive to dopamine receptor agonists. Therefore, to determine the basis of this dopamine supersensitivity, the proportion of dopamine $D2^{High}$ receptors was measured in the striata of mGlu2 and mGlu3 receptor knockout mice. The proportion of $D2^{High}$ receptors was found to be elevated by 220% in the striata of both knockouts. To measure the functional dopamine supersensitivity, the D2 agonist (+)PHNO was used to stimulate the incorporation of GTP-γ-S in the striatal homogenates in the presence of drugs that blocked the dopamine D1, D3, and D5 receptors. Compared with control striata, the mGlu2 receptor knockout tissues were 67-fold more sensitive to (+)PHNO, while the mGlu3 receptor knockout tissues were 17-fold more sensitive. These data suggest that group II mGlu receptors—mGlu2 receptors in particular—may normally regulate D2 receptors by reducing the proportion of high-affinity D2 receptors in membranes. Such regulation may contribute to the antipsychotic action of mGlu2/3 receptor agonists. Synapse 63:247–251, 2009. © 2008 Wiley-Liss, Inc.
File Format	HTM / HTML
ISSN	08874476
Issue Number	3
Volume Number	63
e-ISSN	10982396
Journal	Synapse
Language	English
Publisher	Wiley
Publisher Date	2009-03-01
Publisher Place	United States
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Neurology Corpus Striatum Drug Effects Dopamine Pharmacology Receptors, Ampa Deficiency Receptors, Dopamine D2 Metabolism Receptors, Metabotropic Glutamate Vitamin K 1 Analogs & Derivatives Animals Binding, Competitive Domperidone Pharmacokinetics Dopamine Agonists Dopamine Antagonists Dose-response Relationship, Drug Guanosine 5'-o-(3-thiotriphosphate) Mice Mice, Knockout Oxazines Protein Binding Journal Article Research Support, Non-u.s. Gov't
Alternative Title	Glutamate receptor mGlu2 and mGlu3 knockout striata are dopamine supersensitive, with elevated D2(High) receptors and marked supersensitivity to the dopamine agonist (+)PHNO
Content Type	Text
Resource Type	Article
Subject	Cellular and Molecular Neuroscience

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Glutamate receptor mGlu2 and mGlu3 knockout striata are dopamine supersensitive, with elevated $D2^{High}$ receptors and marked supersensitivity to the dopamine agonist (+)PHNO

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