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Interactive effects of mGlu5 and 5-HT(2A) receptors on locomotor activity in mice

RATIONALE: Metabotropic glutamate (mGlu) receptors have been suggested to play a role in neuropsychiatric disorders including schizophrenia, drug abuse, and depression. Because serotonergic hallucinogens increase glutamate release and mGlu receptors modulate the response to serotonin (5-HT)(2A) acti...

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Autores principales: Halberstadt, Adam L., Lehmann-Masten, Virginia D., Geyer, Mark A., Powell, Susan B.
Formato: Texto
Lenguaje:English
Publicado: Springer-Verlag 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3072483/
https://www.ncbi.nlm.nih.gov/pubmed/21153406
http://dx.doi.org/10.1007/s00213-010-2115-1
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author Halberstadt, Adam L.
Lehmann-Masten, Virginia D.
Geyer, Mark A.
Powell, Susan B.
author_facet Halberstadt, Adam L.
Lehmann-Masten, Virginia D.
Geyer, Mark A.
Powell, Susan B.
author_sort Halberstadt, Adam L.
collection PubMed
description RATIONALE: Metabotropic glutamate (mGlu) receptors have been suggested to play a role in neuropsychiatric disorders including schizophrenia, drug abuse, and depression. Because serotonergic hallucinogens increase glutamate release and mGlu receptors modulate the response to serotonin (5-HT)(2A) activation, the interactions between serotonin 5-HT(2A) receptors and mGlu receptors may prove to be important for our understanding of these diseases. OBJECTIVE: We tested the effects of the serotonergic hallucinogen and 5-HT(2A) agonist, 2,5-dimethoxy-4-methylamphetamine (DOM), and the selective 5-HT(2A) antagonist, M100907, on locomotor activity in the mouse behavioral pattern monitor (BPM) in mGlu5 wild-type (WT) and knockout (KO) mice on a C57 background. RESULTS: Both male and female mGlu5 KO mice showed locomotor hyperactivity and diminished locomotor habituation compared with their WT counterparts. Similarly, the mGlu5-negative allosteric modulator 2-methyl-6-(phenylethynyl)pyridine (MPEP) also increased locomotor hyperactivity, which was absent in mGlu5 KO mice. The locomotor hyperactivity in mGlu5 receptor KO mice was potentiated by DOM (0.5 mg/kg, subcutaneously (SC)) and attenuated by M100907 (1.0 mg/kg, SC). M100907 (0.1 mg/kg, SC) also blocked the hyperactivity induced by MPEP. CONCLUSIONS: These studies demonstrated that loss of mGlu5 receptor activity either pharmacologically or through gene deletion leads to locomotor hyperactivity in mice. Additionally, the gene deletion of mGlu5 receptors increased the behavioral response to the 5-HT(2A) agonist DOM, suggesting that mGlu5 receptors either mitigate the behavioral effects of 5-HT(2A) hallucinogens or that mGlu5 KO mice show an increased sensitivity to 5-HT(2A) agonists. Taken together, these studies indicate a functional interaction between mGlu5 and 5-HT(2A) receptors.
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spelling pubmed-30724832011-05-18 Interactive effects of mGlu5 and 5-HT(2A) receptors on locomotor activity in mice Halberstadt, Adam L. Lehmann-Masten, Virginia D. Geyer, Mark A. Powell, Susan B. Psychopharmacology (Berl) Original Investigation RATIONALE: Metabotropic glutamate (mGlu) receptors have been suggested to play a role in neuropsychiatric disorders including schizophrenia, drug abuse, and depression. Because serotonergic hallucinogens increase glutamate release and mGlu receptors modulate the response to serotonin (5-HT)(2A) activation, the interactions between serotonin 5-HT(2A) receptors and mGlu receptors may prove to be important for our understanding of these diseases. OBJECTIVE: We tested the effects of the serotonergic hallucinogen and 5-HT(2A) agonist, 2,5-dimethoxy-4-methylamphetamine (DOM), and the selective 5-HT(2A) antagonist, M100907, on locomotor activity in the mouse behavioral pattern monitor (BPM) in mGlu5 wild-type (WT) and knockout (KO) mice on a C57 background. RESULTS: Both male and female mGlu5 KO mice showed locomotor hyperactivity and diminished locomotor habituation compared with their WT counterparts. Similarly, the mGlu5-negative allosteric modulator 2-methyl-6-(phenylethynyl)pyridine (MPEP) also increased locomotor hyperactivity, which was absent in mGlu5 KO mice. The locomotor hyperactivity in mGlu5 receptor KO mice was potentiated by DOM (0.5 mg/kg, subcutaneously (SC)) and attenuated by M100907 (1.0 mg/kg, SC). M100907 (0.1 mg/kg, SC) also blocked the hyperactivity induced by MPEP. CONCLUSIONS: These studies demonstrated that loss of mGlu5 receptor activity either pharmacologically or through gene deletion leads to locomotor hyperactivity in mice. Additionally, the gene deletion of mGlu5 receptors increased the behavioral response to the 5-HT(2A) agonist DOM, suggesting that mGlu5 receptors either mitigate the behavioral effects of 5-HT(2A) hallucinogens or that mGlu5 KO mice show an increased sensitivity to 5-HT(2A) agonists. Taken together, these studies indicate a functional interaction between mGlu5 and 5-HT(2A) receptors. Springer-Verlag 2010-12-10 2011 /pmc/articles/PMC3072483/ /pubmed/21153406 http://dx.doi.org/10.1007/s00213-010-2115-1 Text en © The Author(s) 2010 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Original Investigation
Halberstadt, Adam L.
Lehmann-Masten, Virginia D.
Geyer, Mark A.
Powell, Susan B.
Interactive effects of mGlu5 and 5-HT(2A) receptors on locomotor activity in mice
title Interactive effects of mGlu5 and 5-HT(2A) receptors on locomotor activity in mice
title_full Interactive effects of mGlu5 and 5-HT(2A) receptors on locomotor activity in mice
title_fullStr Interactive effects of mGlu5 and 5-HT(2A) receptors on locomotor activity in mice
title_full_unstemmed Interactive effects of mGlu5 and 5-HT(2A) receptors on locomotor activity in mice
title_short Interactive effects of mGlu5 and 5-HT(2A) receptors on locomotor activity in mice
title_sort interactive effects of mglu5 and 5-ht(2a) receptors on locomotor activity in mice
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3072483/
https://www.ncbi.nlm.nih.gov/pubmed/21153406
http://dx.doi.org/10.1007/s00213-010-2115-1
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