ArticleBiological psychiatry2023
Habenular Neurons Expressing Mu Opioid Receptors Promote Negative Affect in a Projection-Specific Manner.
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 27 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 26 citations in OpenAlex.
- Multi-omic spatial mapping of the human habenula defines the molecular and anatomical organization of medial and lateral subregions.bioRxiv : the preprint server for biology · 2026Article
- Contributions of dorsal medial prefrontal cortex GABAergic mu opioid receptors on acute restraint stress-induced anxiety-like behavior.Biology direct · 2026Article
- Transcriptional Response to Chronic Long-Access Fentanyl Self-Administration in Rat Habenula and Amygdala.Addiction biology · 2026Article
- Targeting Mu Opioid Receptor Neurons of the Habenula to Limit Naloxone Aversion.Biological psychiatry · 2026Article
- Review: "The Disappointment Dilemma: Short- and Long-Term Learning From Negative Outcomes".The European journal of neuroscience · 2026Review
- Opioid withdrawal engages a habenular subpopulation responsive to aversive states.bioRxiv : the preprint server for biology · 2026Article
- Transcriptional response to chronic long-access fentanyl self-administration in rat habenula and amygdala.bioRxiv : the preprint server for biology · 2025Article
- The neural circuits and signalling pathways of opioid use disorder.Nature reviews. Neuroscience · 2025Review
- Nicotinic Receptors in the Medial Habenula to Interpeduncular Nucleus Pathway: Modulators of Reward, Aversion and Emotion.The European journal of neuroscience · 2025Review
- Transcriptomic Analysis of the Human Habenula in Schizophrenia.The American journal of psychiatry · 2025Article
- Mu-opioid receptor activation potentiates excitatory transmission at the habenulo-peduncular synapse.Cell reports · 2025Article
- GPR139, an Ancient Receptor and an Emerging Target for Neuropsychiatric and Behavioral Disorders.Molecular neurobiology · 2025Review
- Disrupted maternal behavior in morphine-dependent pregnant rats and anhedonia in their offspring.Neuropharmacology · 2025Article
- Opioid Regulation of Social Homeostasis: Connecting Loneliness to Addiction.Biological psychiatry · 2025Review
- VTA µ-Opioidergic Neurons Facilitate Low Sociability in Protracted Opioid Abstinence.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Disrupted Maternal Behavior in Morphine-Dependent Pregnant Rats and Anhedonia in their Offspring.bioRxiv : the preprint server for biology · 2024Article
- VTA μ-opioidergic neurons facilitate low sociability in protracted opioid withdrawal.bioRxiv : the preprint server for biology · 2024Article
- A master regulator of opioid reward in the ventral prefrontal cortex.Science (New York, N.Y.) · 2024Article
- Article
- Model of negative affect induced by withdrawal from acute and chronic morphine administration in male mice.Scientific reports · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundThe mu opioid receptor (MOR) is central to hedonic balance and produces euphoria by engaging reward circuits. MOR signaling may also influence aversion centers, notably the habenula (Hb), where the receptor is highly dense. Our previous data suggest that the inhibitory activity of MOR in the Hb may limit aversive states. To investigate this hypothesis, we tested whether neurons expressing MOR in the Hb (Hb-MOR neurons) promote negative affect.
methodsUsing Oprm1-Cre knockin mice, we combined tracing and optogenetics with behavioral testing to investigate consequences of Hb-MOR neuron stimulation for approach/avoidance (real-time place preference), anxiety-related responses (open field, elevated plus maze, and marble burying), and despair-like behavior (tail suspension).
resultsOptostimulation of Hb-MOR neurons elicited avoidance behavior, demonstrating that these neurons promote aversive states. Anterograde tracing showed that, in addition to the interpeduncular nucleus, Hb-MOR neurons project to the dorsal raphe nucleus. Optostimulation of Hb-MOR/interpeduncular nucleus terminals triggered avoidance and despair-like responses with no anxiety-related effect, whereas light-activation of Hb-MOR/dorsal raphe nucleus terminals increased levels of anxiety with no effect on other behaviors, revealing 2 dissociable pathways controlling negative affect.
conclusionsTogether, the data demonstrate that Hb neurons expressing MOR facilitate aversive states via 2 distinct Hb circuits, contributing to despair-like behavior (Hb-MOR/interpeduncular nucleus) and anxiety (Hb-MOR/dorsal raphe nucleus). The findings support the notion that inhibition of these neurons by either endogenous or exogenous opioids may relieve negative affect, a mechanism that would have implications for hedonic homeostasis and addiction.
Indexed as
Identifiers
What OpenQuestion holds
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.