ArticleBiological psychiatry2023
Mu Opioid Receptor-Positive Neurons in the Dorsal Raphe Nucleus Are Impaired by Morphine Abstinence.
Article in Biological psychiatry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
- Targeting Mu Opioid Receptor Neurons of the Habenula to Limit Naloxone Aversion.Biological psychiatry · 2026Article
- Corticostriatal cocaine-seeking ensembles are defined by differing gene expression from sucrose-seeking ensembles using a within-subject dual self-administration and seeking mouse model.Addiction neuroscience · 2025Article
- The neural circuits and signalling pathways of opioid use disorder.Nature reviews. Neuroscience · 2025Review
- Nonclinical human neural new approach methodologies (NAMs): Electrophysiological assessment of opioid agonist and antagonist combination.NAM journal · 2025Article
- VTA µ-Opioidergic Neurons Facilitate Low Sociability in Protracted Opioid Abstinence.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Article
- Incubation of social deficit during morphine abstinence in male mice using a novel unbiased and automatized method.Frontiers in behavioral neuroscience · 2025Article
- The role of dorsal raphe nucleus neuropeptides in reward and aversion.Frontiers in behavioral neuroscience · 2025Review
- Chronic Morphine Leaves a Durable Fingerprint on Whole-Brain Functional Connectivity.Biological psychiatry · 2024Article
- VTA μ-opioidergic neurons facilitate low sociability in protracted opioid withdrawal.bioRxiv : the preprint server for biology · 2024Article
- Selective targeting of mu opioid receptors to primary cilia.Cell reports · 2024Article
- Opioidergic tuning of social attachment: reciprocal relationship between social deprivation and opioid abuse.Frontiers in neuroanatomy · 2024Review
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundChronic opioid exposure leads to hedonic deficits and enhanced vulnerability to addiction, which are observed and even strengthen after a period of abstinence, but the underlying circuit mechanisms are poorly understood. In this study, using both molecular and behavioral approaches, we tested the hypothesis that neurons expressing mu opioid receptors (MORs) in the dorsal raphe nucleus (DRN) are involved in addiction vulnerability associated with morphine abstinence.
methodsMOR-Cre mice were exposed to chronic morphine and then went through spontaneous withdrawal for 4 weeks, a well-established mouse model of morphine abstinence. We studied DRN-MOR neurons of abstinent mice using 1) viral translating ribosome affinity for transcriptome profiling, 2) fiber photometry to measure neuronal activity, and 3) an opto-intracranial self-stimulation paradigm applied to DRN-MOR neurons to assess responses related to addiction vulnerability including persistence to respond, motivation to obtain the stimulation, self-stimulation despite punishment, and cue-induced reinstatement.
resultsDRN-MOR neurons of abstinent animals showed a downregulation of genes involved in ion conductance and MOR-mediated signaling, as well as altered responding to acute morphine. Opto-intracranial self-stimulation data showed that abstinent animals executed more impulsive-like and persistent responses during acquisition and scored higher on addiction-like criteria.
conclusionsOur data suggest that protracted abstinence to chronic morphine leads to reduced MOR function in DRN-MOR neurons and abnormal self-stimulation of these neurons. We propose that DRN-MOR neurons have partially lost their reward-facilitating properties, which in turn may lead to increased propensity to perform addiction-related behaviors.
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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.