ArticleAddiction biology2017
Ethanol drives aversive conditioning through dopamine 1 receptor and glutamate receptor-mediated activation of lateral habenula neurons.
Article in Addiction biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 52 citations in OpenAlex.
- Stressed Avoider rats show blunted sensitivity to alcohol's aversive effects: Potential contributions of the lateral habenula and lateral hypothalamus.bioRxiv : the preprint server for biology · 2025Article
- Article
- The lateral habenula is not required for ethanol dependence-induced escalation of drinking.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Article
- Exploring the Role of Orexinergic Neurons in Parkinson's Disease.Neurotoxicity research · 2021Review
- Roles of corticotropin-releasing factor signaling in the lateral habenula in anxiety-like and alcohol drinking behaviors in male rats.Neurobiology of stress · 2021Article
- Acetaldehyde Excitation of Lateral Habenular Neurons via Multiple Cellular Mechanisms.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Endocannabinoid signaling in the lateral habenula regulates pain and alcohol consumption.Translational psychiatry · 2021Article
- The Emerging Role of LHb CaMKII in the Comorbidity of Depressive and Alcohol Use Disorders.International journal of molecular sciences · 2020Review
- Circuits and functions of the lateral habenula in health and in disease.Nature reviews. Neuroscience · 2020Review
- Environmental enrichment decreases chronic psychosocial stress-impaired extinction and reinstatement of ethanol conditioned place preference in C57BL/6 male mice.Psychopharmacology · 2020Article
- Activation of glycine receptors in the lateral habenula rescues anxiety- and depression-like behaviors associated with alcohol withdrawal and reduces alcohol intake in rats.Neuropharmacology · 2019Article
- Alcohol withdrawal drives depressive behaviors by activating neurons in the rostromedial tegmental nucleus.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2019Article
- Elevation of Transient Receptor Potential Vanilloid 1 Function in the Lateral Habenula Mediates Aversive Behaviors in Alcohol-withdrawn Rats.Anesthesiology · 2019Article
- Calcium/calmodulin-stimulated adenylyl cyclases 1 and 8 regulate reward-related brain activity and ethanol consumption.Brain imaging and behavior · 2019Article
- Downregulation of M-channels in lateral habenula mediates hyperalgesia during alcohol withdrawal in rats.Scientific reports · 2019Article
- Anterior Insular Cortex is Critical for the Propensity to Relapse Following Punishment-Imposed Abstinence of Alcohol Seeking.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Rescue of glutamate transport in the lateral habenula alleviates depression- and anxiety-like behaviors in ethanol-withdrawn rats.Neuropharmacology · 2018Article
- A Focus on Reward Prediction and the Lateral Habenula: Functional Alterations and the Behavioral Outcomes Induced by Drugs of Abuse.Frontiers in synaptic neuroscience · 2018Review
- Review of the cytology and connections of the lateral habenula, an avatar of adaptive behaving.Pharmacology, biochemistry, and behavior · 2017Review
- Ethanol Withdrawal Drives Anxiety-Related Behaviors by Reducing M-type Potassium Channel Activity in the Lateral Habenula.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
There has been increasing interest in the lateral habenula (LHb) given its potent regulatory role in many aversion-related behaviors. Interestingly, ethanol can be rewarding as well as aversive; we therefore investigated whether ethanol exposure alters pacemaker firing or glutamate receptor signaling in LHb neurons in vitro and also whether LHb activity in vivo might contribute to the acquisition of conditioned place aversion to ethanol. Surprisingly, in epithalamic slices, low doses of ethanol (1.4 mM) strongly accelerated LHb neuron firing (by ~60%), and ethanol's effects were much reduced by blocking glutamate receptors. Ethanol increased presynaptic glutamate release, and about half of this effect was mediated by dopamine subtype 1 receptors (D1Rs) and cyclic adenosine monophosphate (cAMP)-dependent signaling pathways. In agreement with these findings, c-Fos immunoreactivity in LHb regions was enhanced after a single administration of a low dose of ethanol (0.25 g/kg i.p.). Importantly, the same dose of ethanol in vivo also produced strong conditioned place aversion, and this was prevented by inhibiting D1Rs or neuronal activity within the LHb. By contrast, a higher dose (2 g/kg) led to ethanol conditioned place preference, which was enhanced by inhibiting neuronal activity or D1Rs within the LHb and suppressed by infusing aminomethylphosphonic acid or the D1R agonist SKF38393 within the LHb. Our in vitro and in vivo observations show, for the first time, that ethanol increases LHb excitation, mediated by D1R and glutamate receptors, and may underlie a LHb aversive signal that contributes to ethanol-related aversion.
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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.