Intracerebroventricular (i.c.v.) injection of phospholipase C inhibitors and structurally dissimilar PKC inhibitors were shown to completely reverse morphine antinociceptive tolerance in mice. Since Group I metabotropic glutamate receptors (mGlu(1) and mGlu(5)) activate phospholipase C through Galpha(q) Galpha(11) proteins, we hypothesized that morphine tolerance could occur through an increase in mGlu(1) and mGlu(5) receptor stimulation. Seventy-two hours after implantation of placebo or 75 mg morphine pellets, mice were tested in the 56 degrees C warm-water tail-withdrawal test following i.c.v. injection of vehicle or test drug. The mGlu(1) receptor antagonist CPCCOEt (7-(Hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester) partly but significantly reversed morphine tolerance. The mGlu(5) receptor antagonist MPEP (2-Methyl-6-(phenylethynyl)pyridine hydrochloride) also partly reversed the antinociceptive tolerance. Co-administering CPCCOEt with MPEP completely reversed the tolerance. Furthermore, the mixed mGlu(1)/mGlu(5) antagonist AIDA ((RS)-1-Aminoindan-1,5-dicarboxylic acid) also completely reversed the tolerance. Thus, greater mGlu(1) and mGlu(5) receptor stimulation during morphine tolerance may lead to persistent activation of the phosphatidylinositol cascade.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ejphar.2004.03.055 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Parvalbumin interneuron mGlu receptors govern sex differences in prefrontal cortex physiology and binge drinking.
Neuropsychopharmacology
November 2024
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
Despite established sex differences in the prevalence and presentation of psychiatric disorders, little is known about the cellular and synaptic mechanisms that guide these differences under basal conditions. The proper function of the prefrontal cortex (PFC) is essential for the top-down regulation of motivated behaviors. The activity of the PFC is tightly controlled by parvalbumin-expressing interneurons (PV-INs), a key subpopulation of fast-spiking GABAergic cells that regulate cortical excitability through direct innervations onto the perisomatic regions of nearby pyramidal cells.
View Article and Find Full Text PDFParvalbumin interneuron mGlu receptors govern sex differences in prefrontal cortex physiology and binge drinking.
bioRxiv
March 2024
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, 15219, USA.
Despite established sex differences in the prevalence and presentation of psychiatric disorders, little is known about the cellular and synaptic mechanisms that guide these differences under basal conditions. Proper function of the prefrontal cortex (PFC) is essential for the top-down regulation of motivated behaviors. Activity of the PFC is tightly controlled by parvalbumin-expressing interneurons (PV-INs), a key subpopulation of fast-spiking GABAergic cells that regulate cortical excitability through direct innervations onto the perisomatic regions of nearby pyramidal cells.
View Article and Find Full Text PDFGroup I and group II metabotropic glutamate receptors are upregulated in the synapses of infant rats prenatally exposed to valproic acid.
Psychopharmacology (Berl)
December 2023
Institute for Biomedical Research and Innovation, National Research Council (IRIB-CNR), Catania, Italy.
Rationale: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interaction and restricted/stereotyped behavior. Prenatal exposure to valproic acid (VPA) is associated with an increased risk of developing ASD in humans and autistic-like behaviors in rodents. Increasing evidence indicates that dysfunctions of glutamate receptors at synapses are associated with ASD.
View Article and Find Full Text PDFGroup I mGluRs positive allosteric modulators improved schizophrenia-related behavioral and molecular deficits in the Poly I:C rat model.
Pharmacol Biochem Behav
August 2023
Department of Physiology, Faculty of Medicine, Erciyes University, Kayseri, Türkiye. Electronic address:
Article Synopsis
- Maternal exposure to Poly I:C increases proinflammatory cytokines and induces schizophrenia-like symptoms in offspring, leading to the exploration of mGluR as a therapeutic target.
- The study aimed to assess behavioral and molecular changes in a rat model of schizophrenia, using both positive and negative allosteric modulators of mGlu1 and mGlu5 receptors.
- Results indicated that positive allosteric modulators improved behavioral outcomes and reduced proinflammatory cytokine levels, suggesting mGlu5 receptor PAMs like VU-29 could be potential treatments for schizophrenia.
GPCR interactions involving metabotropic glutamate receptors and their relevance to the pathophysiology and treatment of CNS disorders.
Neuropharmacology
September 2023
Translational Neuroscience Program, Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, 15219, USA.
Cellular responses to metabotropic glutamate (mGlu) receptor activation are shaped by mechanisms of receptor-receptor interaction. mGlu receptor subtypes form homodimers, intra- or inter-group heterodimers, and heteromeric complexes with other G protein-coupled receptors (GPCRs). In addition, mGlu receptors may functionally interact with other receptors through the βγ subunits released from G proteins in response to receptor activation or other mechanisms.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!