ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Morphine withdrawal enhances constitutive μ-opioid receptor activity in the ventral tegmental area.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 53 citations in OpenAlex.
- Chronic morphine differentially impacts glutamatergic synaptic plasticity in the ventral tegmental area of adult versus adolescent mice.Neuropharmacology · 2026Article
- The Impact of Levetiracetam on Various Symptoms of Morphine Dependence in Mice.Life (Basel, Switzerland) · 2026Article
- AI-derived therapeutic development of a serotonin receptor-targeting drug for the treatment of opioid use disorder.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Review
- Divergent opioid-mediated suppression of inhibition between hippocampus and neocortex across species and development.Neuron · 2025Article
- Divergent opioid-mediated suppression of inhibition between hippocampus and neocortex across species and development.bioRxiv : the preprint server for biology · 2025Article
- Molecular and cellular basis of mu-opioid receptor signaling: mechanisms underlying tolerance and dependence development.Frontiers in neuroscience · 2025Review
- Opioid-induced neuroanatomical, microglial and behavioral changes are blocked by suvorexant without diminishing opioid analgesia.Nature. Mental health · 2024Article
- Studying Synaptic Connectivity and Strength with Optogenetics and Patch-Clamp Electrophysiology.International journal of molecular sciences · 2022Review
- Molecular mechanism of agonism and inverse agonism in ghrelin receptor.Nature communications · 2022Article
- Goofballing of Opioid and Methamphetamine: The Science Behind the Deadly Cocktail.Frontiers in pharmacology · 2022Review
- Pain-induced impulsivity is sexually dimorphic and mu-opioid receptor sensitive in rats.Psychopharmacology · 2021Article
- Pleasure, addiction, and hypocretin (orexin).Handbook of clinical neurology · 2021Review
- The molecular neurobiology and neuropathology of opioid use disorder.Current research in neurobiology · 2021Article
- GRK2 Dictates a Functional Switch of the Peripheral Mu-Opioid Receptor.ACS chemical neuroscience · 2020Article
- The Mechanisms Involved in Morphine Addiction: An Overview.International journal of molecular sciences · 2019Review
- Molecular Adaptations in the Rat Dorsal Striatum and Hippocampus Following Abstinence-Induced Incubation of Drug Seeking After Escalated Oxycodone Self-Administration.Molecular neurobiology · 2019Article
- Chemogenetic Manipulations of Ventral Tegmental Area Dopamine Neurons Reveal Multifaceted Roles in Cocaine Abuse.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Dysregulation of Dopaminergic Regulatory Factors TH, Nurr1, and Pitx3 in the Ventral Tegmental Area Associated with Neuronal Injury Induced by Chronic Morphine Dependence.International journal of molecular sciences · 2019Article
- Altered Activity of SK Channel Underpins Morphine Withdrawal Relevant Psychiatric Deficiency in Infralimbic to Accumbens Shell Pathway.Frontiers in psychiatry · 2019Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
μ-Opioid receptors (MORs) in the ventral tegmental area (VTA) are pivotally involved in addictive behavior. While MORs are typically activated by opioids, they can also become constitutively active in the absence of any agonist. In the current study, we present evidence that MOR constitutive activity is highly relevant in the mouse VTA, as it regulates GABAergic input to dopamine neurons. Specifically, suppression of MOR constitutive activity with the inverse agonist KC-2-009 enhanced GABAergic neurotransmission onto VTA dopamine neurons. This inverse agonistic effect was fully blocked by the specific MOR neutral antagonist CTOP, which had no effect on GABAergic transmission itself. We next show that withdrawal from chronic morphine further increases the magnitude of inverse agonistic effects at the MOR, suggesting enhanced MOR constitutive activity. We demonstrate that this increase can be an adaptive response to the detrimental elevation in cAMP levels known to occur during morphine withdrawal. These findings offer important insights in the physiological occurrence and function of MOR constitutive activity, and have important implications for therapeutic strategies aimed at normalizing MOR signaling during addiction and opioid overdose.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.