Dataset Information
Emotional Impairment and Persistent Upregulation of mGlu5 Receptor following Morphine Abstinence: Implications of an mGlu5-MOPr Interaction.
Ontology highlight
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/?-opioid receptor interaction was assessed by performing metabotropic glutamate receptor 5 autoradiographic binding in brains of mice lacking the ?-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 ?-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 ?-opioid receptor system manipulation on metabotropic glutamate receptor 5 binding in the brain.
SUBMITTER: Zanos P
PROVIDER: S-EPMC4966274 | biostudies-literature | 2016 Jul
REPOSITORIES: biostudies-literature
Publications
Emotional Impairment and Persistent Upregulation of mGlu5 Receptor following Morphine Abstinence: Implications of an mGlu5-MOPr Interaction.
The international journal of neuropsychopharmacology 20160705 7
<h4>Background</h4>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.<h4>Methods</h4>Mice were treated with a 7-day escalating-dose morphine administration paradigm. Following withdrawal, the develo ...[more]
