Zanos, P; Georgiou, P; Gonzalez, LR; Hourani, S; Chen, Y; Kitchen, I; Kieffer, BL; Winsky-Sommerer, R; Bailey, A
(2016)
Emotional Impairment and Persistent Upregulation of mGlu5 Receptor following Morphine Abstinence: Implications of an mGlu5-MOPr Interaction.
The International Journal of Neuropsychopharmacology, 19 (7).
ISSN 1469-5111
https://doi.org/10.1093/ijnp/pyw011
SGUL Authors: Bailey, Alexis
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Abstract
BACKGROUND: A difficult problem in treating opioid addicts is the maintenance of a drug-free state because of the negative emotional symptoms associated with withdrawal, which may trigger relapse. Several lines of evidence suggest a role for the metabotropic glutamate receptor 5 in opioid addiction; however, its involvement during opioid withdrawal is not clear. METHODS: Mice were treated with a 7-day escalating-dose morphine administration paradigm. Following withdrawal, the development of affective behaviors was assessed using the 3-chambered box, open-field, elevated plus-maze and forced-swim tests. Metabotropic glutamate receptor 5 autoradiographic binding was performed in mouse brains undergoing chronic morphine treatment and 7 days withdrawal. Moreover, since there is evidence showing direct effects of opioid drugs on the metabotropic glutamate receptor 5 system, the presence of an metabotropic glutamate receptor 5/μ-opioid receptor interaction was assessed by performing metabotropic glutamate receptor 5 autoradiographic binding in brains of mice lacking the μ-opioid receptor gene. RESULTS: Withdrawal from chronic morphine administration induced anxiety-like, depressive-like, and impaired sociability behaviors concomitant with a marked upregulation of metabotropic glutamate receptor 5 binding. Administration of the metabotropic glutamate receptor 5 antagonist, 3-((2-Methyl-4-thiazolyl)ethynyl)pyridine, reversed morphine abstinence-induced depressive-like behaviors. A brain region-specific increase in metabotropic glutamate receptor 5 binding was observed in the nucleus accumbens shell, thalamus, hypothalamus, and amygdala of μ-opioid receptor knockout mice compared with controls. CONCLUSIONS: These results suggest an association between metabotropic glutamate receptor 5 alterations and the emergence of opioid withdrawal-related affective behaviors. This study supports metabotropic glutamate receptor 5 system as a target for the development of pharmacotherapies for the treatment of opioid addiction. Moreover, our data show direct effects of μ-opioid receptor system manipulation on metabotropic glutamate receptor 5 binding in the brain.
Item Type: | Article | |||||||||
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Additional Information: | © The Author 2016. Published by Oxford University Press on behalf of CINP. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com | |||||||||
Keywords: | Morphine, mGlu5R, opioids, withdrawal, μ-opioid receptor, Psychiatry, 11 Medical And Health Sciences, 17 Psychology And Cognitive Sciences | |||||||||
SGUL Research Institute / Research Centre: | Academic Structure > Institute of Medical, Biomedical and Allied Health Education (IMBE) Academic Structure > Institute of Medical, Biomedical and Allied Health Education (IMBE) > Centre for Biomedical Education (INMEBE) |
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Journal or Publication Title: | The International Journal of Neuropsychopharmacology | |||||||||
ISSN: | 1469-5111 | |||||||||
Language: | ENG | |||||||||
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PubMed ID: | 26861145 | |||||||||
Go to PubMed abstract | ||||||||||
URI: | https://openaccess.sgul.ac.uk/id/eprint/108001 | |||||||||
Publisher's version: | https://doi.org/10.1093/ijnp/pyw011 |
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