ArticleJournal of neurochemistry2014
Mu-opioid receptor splice variants: sex-dependent regulation by chronic morphine.
Article in Journal of neurochemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- The actions of morphine on microglia and the underlying effects on associated adverse effects.Psychopharmacology · 2026Review
- Narrative review of the scientific and methodological explanations for 101 mechanisms of opioid tolerance.Pain reports · 2025Article
- Molecular and cellular basis of mu-opioid receptor signaling: mechanisms underlying tolerance and dependence development.Frontiers in neuroscience · 2025Review
- Epigenetic and sex differences in opioid use disorder in chronic pain: A real-world study linked with OPRM1 DNA methylation.Addiction biology · 2024Article
- Amelioration of morphine withdrawal syndrome by systemic and intranasal administration of mesenchymal stem cell-derived secretome in preclinical models of morphine dependence.CNS neuroscience & therapeutics · 2024Article
- Mechanism of opioid addiction and its intervention therapy: Focusing on the reward circuitry and mu-opioid receptor.MedComm · 2022Review
- Dysregulated expression of the alternatively spliced variant mRNAs of the mu opioid receptor gene, OPRM1, in the medial prefrontal cortex of male human heroin abusers and heroin self-administering male rats.Journal of neuroscience research · 2022Article
- G-Protein-Coupled Estrogen Receptor (GPER) in the Rostral Ventromedial Medulla Is Essential for Mobilizing Descending Inhibition of Itch.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Relevance of Mu-Opioid Receptor Splice Variants and Plasticity of Their Signaling Sequelae to Opioid Analgesic Tolerance.Cellular and molecular neurobiology · 2021Review
- Mu Opioids Induce Biased Signaling at the Full-Length Seven Transmembrane C-Terminal Splice Variants of the mu Opioid Receptor Gene, Oprm1.Cellular and molecular neurobiology · 2021Article
- Increased functional coupling of the mu opioid receptor in the anterior insula of depressed individuals.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Article
- Abuse Liability, Anti-Nociceptive, and Discriminative Stimulus Properties of IBNtxA.ACS pharmacology & translational science · 2020Article
- Sex and Gender Differences in the Effects of Novel Psychoactive Substances.Brain sciences · 2020Review
- Phosphorylation of unique C-terminal sites of the mu-opioid receptor variants 1B2 and 1C1 influences their Gs association following chronic morphine.Journal of neurochemistry · 2020Article
- Genomewide Gene-by-Sex Interaction Scans Identify ADGRV1 for Sex Differences in Opioid Dependent African Americans.Scientific reports · 2019Observational
- Morphine-induced MOR-1X and ASF/SF2 Expressions Are Independent of Transcriptional Regulation: Implications for MOR-1X Signaling.Journal of cellular physiology · 2016Article
- Regulation and Functional Implications of Opioid Receptor Splicing in Opioid Pharmacology and HIV Pathogenesis.Journal of cellular physiology · 2016Review
- Exposure to opiates in female adolescents alters mu opiate receptor expression and increases the rewarding effects of morphine in future offspring.Neuropharmacology · 2016Article
- Contribution of Endogenous Spinal Endomorphin 2 to Intrathecal Opioid Antinociception in Rats Is Agonist Dependent and Sexually Dimorphic.The journal of pain · 2015Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The gene encoding the mu-opioid receptor (MOR) generates a remarkable diversity of subtypes, the functional significance of which remains largely unknown. The structure of MOR could be a critical determinant of MOR functionality and its adaptations to chronic morphine exposure. As MOR antinociception has sexually dimorphic dimensions, we determined the influence of sex, stage of estrus cycle, and chronic systemic morphine on levels of MOR splice variant mRNA in rat spinal cord. Chronic systemic morphine influenced the spinal expression of mRNA encoding rMOR-1B2 and rMOR-1C1 in a profoundly sex-dependent fashion. In males, chronic morphine resulted in a twofold increase in expression levels of rMOR-1B2 and rMOR-1C1 mRNA. This effect of chronic morphine was completely absent in females. Increased density of MOR protein in spinal cord of males accompanied the chronic morphine-induced increase in MOR variant mRNA, suggesting that it reflected an increase in corresponding receptor protein. These results suggest that tolerance/dependence results, at least in part, from different adaptational strategies in males and females. The signaling consequences of the unique composition of the C-terminus tip of rMOR-1C1 and rMOR-1B2 could point the way to defining the molecular components of sex-dependent tolerance and withdrawal mechanisms. Chronic systemic morphine increases levels of mRNA encoding two splice variants of mu-opioid receptor (MOR), MOR-1B2 and MOR-1C1, variants differing from rMOR-1 in their C-terminal (and phosphorylation sites therein) and thus possibly signaling sequelae. This adaptation is sex-specific. It occurs in the spinal cord of males, but not females, indicating the importance of sex-specific mechanisms for and treatments of tolerance and addiction.
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Registered trials
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