ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2020
Mu opioid receptors in the medial habenula contribute to naloxone aversion.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 69 citations in OpenAlex.
- Bed Nucleus of the Stria Terminalis PACAP Signaling in the Dorsal Medial Habenula Mediates Depression-Related Behavioral Responses After Chronic Stress.Biological psychiatry · 2026Article
- Transcriptional Response to Chronic Long-Access Fentanyl Self-Administration in Rat Habenula and Amygdala.Addiction biology · 2026Article
- Mu Opioid Receptor mRNA and Protein Localization Across the Rat and Mouse Habenula.The Journal of comparative neurology · 2026Article
- Targeting Mu Opioid Receptor Neurons of the Habenula to Limit Naloxone Aversion.Biological psychiatry · 2026Article
- Opioid withdrawal engages a habenular subpopulation responsive to aversive states.bioRxiv : the preprint server for biology · 2026Article
- Mu opioid receptor mRNA and protein localization across the rat and mouse habenula.bioRxiv : the preprint server for biology · 2025Article
- Transcriptional response to chronic long-access fentanyl self-administration in rat habenula and amygdala.bioRxiv : the preprint server for biology · 2025Article
- Article
- Nicotinic Receptors in the Medial Habenula to Interpeduncular Nucleus Pathway: Modulators of Reward, Aversion and Emotion.The European journal of neuroscience · 2025Review
- Complex opioid driven modulation of glutamatergic and cholinergic neurotransmission in a GABAergic brain nucleus associated with emotion, reward and addiction.bioRxiv : the preprint server for biology · 2025Article
- Mu-opioid receptor activation potentiates excitatory transmission at the habenulo-peduncular synapse.Cell reports · 2025Article
- A small molecule PKCε inhibitor reduces hyperalgesia induced by paclitaxel or opioid withdrawal.JCI insight · 2025Article
- Preconception opioids interact with mouse strain to alter morphine withdrawal in the next generation.Psychopharmacology · 2024Article
- Genetic mouse models in opioid research: current status and future directions.Journal of neural transmission (Vienna, Austria : 1996) · 2024Review
- Model of negative affect induced by withdrawal from acute and chronic morphine administration in male mice.Scientific reports · 2024Article
- Article
- Manipulating ΔFOSB in D1-Type Medium Spiny Neurons of the Nucleus Accumbens Reshapes Whole-Brain Functional Connectivity.Biological psychiatry · 2024Article
- Opioidergic tuning of social attachment: reciprocal relationship between social deprivation and opioid abuse.Frontiers in neuroanatomy · 2024Review
- Cell-type specific molecular architecture for mu opioid receptor function in pain and addiction circuits.Neuropharmacology · 2023Review
- Opioid withdrawal: role in addiction and neural mechanisms.Psychopharmacology · 2023Review
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
The medial habenula (MHb) is considered a brain center regulating aversive states. The mu opioid receptor (MOR) has been traditionally studied at the level of nociceptive and mesolimbic circuits, for key roles in pain relief and reward processing. MOR is also densely expressed in MHb, however, MOR function at this brain site is virtually unknown. Here we tested the hypothesis that MOR in the MHb (MHb-MOR) also regulates aversion processing. We used chnrb4-Cre driver mice to delete the Oprm1 gene in chnrb4-neurons, predominantly expressed in the MHb. Conditional mutant (B4MOR) mice showed habenula-specific reduction of MOR expression, restricted to chnrb4-neurons (50% MHb-MORs). We tested B4MOR mice in behavioral assays to evaluate effects of MOR activation by morphine, and MOR blockade by naloxone. Locomotor, analgesic, rewarding, and motivational effects of morphine were preserved in conditional mutants. In contrast, conditioned place aversion (CPA) elicited by naloxone was reduced in both naïve (high dose) and morphine-dependent (low dose) B4MOR mice. Further, physical signs of withdrawal precipitated by either MOR (naloxone) or nicotinic receptor (mecamylamine) blockade were attenuated. These data suggest that MORs expressed in MHb B4-neurons contribute to aversive effects of naloxone, including negative effect and aversive effects of opioid withdrawal. MORs are inhibitory receptors, therefore we propose that endogenous MOR signaling normally inhibits chnrb4-neurons of the MHb and moderates their known aversive activity, which is unmasked upon receptor blockade. Thus, in addition to facilitating reward at several brain sites, tonic MOR activity may also limit aversion within the MHb circuitry.
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