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Role of metabotropic glutamate receptor 5 in the procholinergic effects of neuropsychotherapeutic compounds
Author(s) -
Tzavara Eleni T.,
Wade Mark R.,
Davis Richard J.,
El Khoury MarieAnne,
Nomikos George G.
Publication year - 2008
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20560
Subject(s) - metabotropic glutamate receptor 5 , chemistry , pharmacology , metabotropic receptor , metabotropic glutamate receptor 2 , metabotropic glutamate receptor , metabotropic glutamate receptor 1 , metabotropic glutamate receptor 7 , agonist , receptor , biochemistry , medicine
We investigated the participation of the metabotropic glutamate receptor type 5 (mGluR5) in mediating increases in cortical acetylcholine (ACh) efflux elicited by established or putative neuropsychotherapeutic compounds, using in vivo microdialysis in rats. The norepinephrine transporter inhibitor atomoxetine, the cannabinoid CB1 receptor antagonist SR141716A, the dopamine D1 receptor agonist dihydrexidine, and the atypical antipsychotic clozapine increased cortical ACh (by about 2–3 fold), whereas the mGluR5 antagonist 2‐methyl‐6‐(phenylethynyl)‐pyridine (MPEP) by itself had no effect. The stimulatory effects of atomoxetine, SR141716A and dihydrexidine on cortical ACh were abolished by pretreatment with MPEP. MPEP also attenuated the stimulatory effect of clozapine on ACh efflux. Thus, mGluR5 activation appears to be involved in the procholinergic effects of compounds that exhibit therapeutic properties or potential in neuropsychiatry. Synapse 62:940–943, 2008. © 2008 Wiley‐Liss, Inc.