ArticleAddiction biology2019
Mu opioid receptors in GABAergic neurons of the forebrain promote alcohol reward and drinking.
Article in Addiction biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 41 citations in OpenAlex.
- An analysis of the effect of mu-opioid receptor gene (OPRM1) promoter region DNA methylation on the response of naltrexone treatment of alcohol dependence.The pharmacogenomics journal · 2020Trial
- Epigenetic mechanisms of HIV and opioid-induced neuropathology: Potential therapies and interventions.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Chronic administration of methocinnamox, a mu-opioid receptor antagonist, reduces hedonic response without impacting motivation in mice.Psychopharmacology · 2025Article
- Genomic and Behavioral Signatures of Selection for Ethanol Preference from the Heterogeneous Stock Collaborative Cross Mice - The Central Nucleus of the Amygdala.Addiction neuroscience · 2025Article
- Mu-opioid receptor knockout on Foxp2-expressing neurons reduces aversion-resistant alcohol drinking.Pharmacology, biochemistry, and behavior · 2025Article
- Mu opioid receptor activation in microglia enhances HIV-1 infection and HIV-infection-induced inflammatory responses.Frontiers in immunology · 2025Article
- Genetic mouse models in opioid research: current status and future directions.Journal of neural transmission (Vienna, Austria : 1996) · 2024Review
- The Roles of Endogenous D2R Dopamine and μ-opioid Receptors of the Brain in Alcohol use Disorder.Current medicinal chemistry · 2024Review
- Investigating the Influence of Morphine and Cocaine on the Mesolimbic Pathway Using a Novel Microimaging Platform.International journal of molecular sciences · 2023Article
- Habenular Neurons Expressing Mu Opioid Receptors Promote Negative Affect in a Projection-Specific Manner.Biological psychiatry · 2023Article
- Genetic and epigenetic studies of opioid abuse disorder - the potential for future diagnostics.Expert review of molecular diagnostics · 2023Review
- Opioids, sleep, analgesia and respiratory depression: Their convergence on Mu (μ)-opioid receptors in the parabrachial area.Frontiers in neuroscience · 2023Review
- Mechanisms Underlying Mu Opioid Receptor Effects on Parallel Fiber-Purkinje Cell Synaptic Transmission in Mouse Cerebellar Cortex.Frontiers in synaptic neuroscience · 2022Article
- Mu opioid receptors on vGluT2-expressing glutamatergic neurons modulate opioid reward.Addiction biology · 2021Article
- Mu-Opioid Receptors Expressed in Glutamatergic Neurons are Essential for Morphine Withdrawal.Neuroscience bulletin · 2020Article
- Behavioral, neurobiological, and neurochemical mechanisms of ethanol self-administration: A translational review.Pharmacology & therapeutics · 2020Review
- Mapping of Morphine-InducedFrontiers in neuroanatomy · 2020Article
- Fentanyl Inhibits Air Puff-Evoked Sensory Information Processing in Mouse Cerebellar Neurons RecordedFrontiers in systems neuroscience · 2020Article
- Mu opioid receptors in the medial habenula contribute to naloxone aversion.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2020Article
- Nuclear transcriptional changes in hypothalamus of Pomc enhancer knockout mice after excessive alcohol drinking.Genes, brain, and behavior · 2019Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
Abstract
Mu opioid receptors (MORs) are widely distributed throughout brain reward circuits and their role in drug and social reward is well established. Substantial evidence has implicated MOR and the endogenous opioid system in alcohol reward, but circuit mechanisms of MOR-mediated alcohol reward and intake behavior remain elusive, and have not been investigated by genetic approaches. We recently created conditional knockout (KO) mice targeting the Oprm1 gene in GABAergic forebrain neurons. These mice (Dlx-MOR KO) show a major MOR deletion in the striatum, whereas receptors in midbrain (including the Ventral Tegmental Area or VTA) and hindbrain are intact. Here, we compared alcohol-drinking behavior and rewarding effects in total (MOR KO) and conditional KO mice. Concordant with our previous work, MOR KO mice drank less alcohol in continuous and intermittent two-bottle choice protocols. Remarkably, Dlx-MOR KO mice showed reduced drinking similar to MOR KO mice, demonstrating that MOR in the forebrain is responsible for the observed phenotype. Further, alcohol-induced conditioned place preference was detected in control but not MOR KO mice, indicating that MOR is essential for alcohol reward and again, Dlx-MOR KO recapitulated the MOR KO phenotype. Taste preference and blood alcohol levels were otherwise unchanged in mutant lines. Together, our data demonstrate that MOR expressed in forebrain GABAergic neurons is essential for alcohol reward-driven behaviors, including drinking and place conditioning. Challenging the prevailing VTA-centric hypothesis, this study reveals another mechanism of MOR-mediated alcohol reward and consumption, which does not necessarily require local VTA MORs but rather engages striatal MOR-dependent mechanisms.
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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.