ArticleeNeuro
Systemic and Intra-Habenular Activation of the Orphan G Protein-Coupled Receptor GPR139 Decreases Compulsive-Like Alcohol Drinking and Hyperalgesia in Alcohol-Dependent Rats.
Article in eNeuro. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 59 citations in OpenAlex.
- A Phase 2 Randomized Trial of NBI-1065846 (TAK-041) in Patients With Anhedonia Associated With Major Depressive Disorder: Results of the TERPSIS Study.Journal of clinical psychopharmacologyTrial
- Ivermectin reduces withdrawal-induced alcohol intake in rats: Association with CeA GABAergic enhancement and P2rx4 genetic liability.Neuropharmacology · 2026Article
- Opioid withdrawal engages a habenular subpopulation responsive to aversive states.bioRxiv : the preprint server for biology · 2026Article
- Transcriptomic signatures of the insular cortex in a mouse model of neuropathic pain.Frontiers in molecular neuroscience · 2026Article
- Alcohol use disorder-associated pain: clinical and preclinical evidence.Alcohol (Fayetteville, N.Y.) · 2025Review
- A conceptual framework for the intersection of hyperalgesia and hyperkatifeia in alcohol addiction.Alcohol (Fayetteville, N.Y.) · 2025Review
- Ivermectin Reduces Withdrawal-Induced Alcohol Intake via CeA GABAergic Enhancement.bioRxiv : the preprint server for biology · 2025Article
- Chronic intermittent ethanol produces nociception through endocannabinoid-independent mechanisms in mice.Neuropharmacology · 2025Article
- A Preclinical Alcohol Biobank: Samples from Behaviorally Characterized HS Rats for AUD Research.eNeuro · 2025Article
- Surrogate GPR139 Agonists Reverse Short-Term Startle Habituation Impairment in Larval Zebrafish.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Chronic intermittent ethanol produces nociception through endocannabinoid-independent mechanisms in mice.bioRxiv : the preprint server for biology · 2025Article
- Orphan peptide and G protein-coupled receptor signalling in alcohol use disorder.British journal of pharmacology · 2024Review
- Catechol-O-Methyltransferase inhibition and alcohol use disorder: Evaluating the efficacy of tolcapone in ethanol-dependent rats.Neuropharmacology · 2024Article
- Article
- Chronic Intermittent Ethanol Vapor Exposure Paired with Two-Bottle Choice to Model Alcohol Use Disorder.Journal of visualized experiments : JoVE · 2023Article
- Alcohol self-administration and nicotine withdrawal alter biomarkers of stress and inflammation and prefrontal cortex changes in Gβ subunits.The American journal of drug and alcohol abuse · 2023Article
- Voluntary and forced exposure to ethanol vapor produces similar escalation of alcohol drinking but differential recruitment of brain regions related to stress, habit, and reward in male rats.Neuropharmacology · 2023Article
- Diverse functions associate with non-coding polymorphisms shared between humans and chimpanzees.BMC ecology and evolution · 2022Article
- The role of orphan receptor GPR139 in neuropsychiatric behavior.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Article
- Class A and C GPCR Dimers in Neurodegenerative Diseases.Current neuropharmacology · 2022Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
GPR139 is an orphan G protein-coupled receptor (GPCR) that is expressed mainly in the brain, with the highest expression in the medial habenula. The modulation of GPR139 receptor function has been hypothesized to be beneficial in the treatment of some mental disorders, but behavioral studies have not yet provided causal evidence of the role of GPR139 in brain dysfunction. Because of the high expression of GPR139 in the habenula, a critical brain region in addiction, we hypothesized that GPR139 may play role in alcohol dependence. Thus, we tested the effect of GPR139 receptor activation using the selective, brain-penetrant receptor agonist JNJ-63533054 on addiction-like behaviors in alcohol-dependent male rats. Systemic administration of JNJ-63533054 (30 mg/kg but not 10 mg/kg, p.o.) reversed the escalation of alcohol self-administration in alcohol-dependent rats, without affecting water or saccharin intake in dependent rats or alcohol intake in nondependent rats. Moreover, systemic JNJ-63533054 administration decreased withdrawal-induced hyperalgesia, without affecting somatic signs of alcohol withdrawal. Further analysis demonstrated that JNJ-63533054 was effective only in a subgroup of dependent rats that exhibited compulsive-like alcohol drinking. Finally, site-specific microinjection of JNJ-63533054 in the habenula but not interpeduncular nucleus (IPN) reduced both alcohol self-administration and withdrawal-induced hyperalgesia in dependent rats. These results provide robust preclinical evidence that GPR139 receptor activation reverses key addiction-like behaviors in dependent animals, suggest that GPR139 may be a novel target for the treatment of alcohol use disorder, and demonstrate that GPR139 is functionally relevant in regulating mammalian behavior.
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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.