ArticleNeuron2022
An inhibitory brainstem input to dopamine neurons encodes nicotine aversion.
Article in Neuron, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 47 citations in OpenAlex.
- Dysregulation of local inhibitory inputs onto laterodorsal tegmental nucleus cholinergic neurons drives depression-like behaviors in mice.Molecular psychiatry · 2026Article
- Psilocybin selectively rescues cognitive flexibility impairments caused by aberrant prefrontal error signaling.bioRxiv : the preprint server for biology · 2026Article
- Can implicit associations and approach-avoidance tendencies be observed in both problematic social network use and tobacco use disorder? Evidence from a laboratory study.Addictive behaviors reports · 2026Article
- Deep learning-assisted SERS for detection of propoxate and isopropoxate in E-cigarettes.RSC advances · 2026Article
- Activation of a locus coeruleus to ventral tegmental area noradrenergic pathway blunts binge-like ethanol intake and promotes aversive unconditioned responses in TH-ires-Cre mice.Neuropharmacology · 2026Article
- Chronic nicotine reduces nigral dopaminergic activity and remodels pedunculopontine cholinergic subpopulations.bioRxiv : the preprint server for biology · 2026Article
- Mesoscopic analysis of GABAergic marker expression in acetylcholine neurons in the whole mouse brain.iScience · 2026Article
- Nicotinic Receptors in the Medial Habenula to Interpeduncular Nucleus Pathway: Modulators of Reward, Aversion and Emotion.The European journal of neuroscience · 2025Review
- Nicotine induces abnormal motor coupling through sensitization of a mechanosensory circuit in Caenorhabditis elegans.PLoS biology · 2025Article
- Mesoscopic analysis of GABAergic marker expression in acetylcholine neurons in the whole mouse brain.bioRxiv : the preprint server for biology · 2025Article
- Individual differences in decision-making shape how mesolimbic dopamine regulates choice confidence and change-of-mind.Nature neuroscience · 2025Article
- Nicotine Withdrawal Drives Aversive Behaviors by Recruiting Inhibitory Interpeduncular Nucleus Inputs to the Laterodorsal Tegmentum in Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Nicotine engages a VTA-NAc feedback loop to inhibit amygdala-projecting dopamine neurons and induce anxiety-like behaviors.Nature communications · 2025Article
- Article
- Nicotine and neuronal nicotinic acetylcholine receptors: unraveling the mechanisms of nicotine addiction.Frontiers in neuroscience · 2025Review
- The Role of Nicotine Metabolic Rate on Nicotine Dependence and Rewarding: Nicotine Metabolism in Chinese Male Smokers and Male Mice.Molecular neurobiology · 2024Article
- Impact of Unitary Synaptic Inhibition on Spike Timing in Ventral Tegmental Area Dopamine Neurons.eNeuro · 2024Article
- Acetylcholine Neurons Become Cholinergic during Three Time Windows in the Developing Mouse Brain.eNeuro · 2024Article
- The association of genetic polymorphisms within the dopaminergic system with nicotine dependence: A narrative review.Heliyon · 2024Review
- Protocol for fiber photometry recording from deep brain regions in head-fixed mice.STAR protocols · 2024Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Nicotine stimulates the dopamine (DA) system, which is essential for its rewarding effect. Nicotine is also aversive at high doses; yet, our knowledge about nicotine's dose-dependent effects on DA circuits remains limited. Here, we demonstrate that high doses of nicotine, which induce aversion-related behavior in mice, cause biphasic inhibitory and excitatory responses in VTA DA neurons that can be dissociated by distinct projections to lateral and medial nucleus accumben subregions, respectively. Guided by computational modeling, we performed a pharmacological investigation to establish that inhibitory effects of aversive nicotine involve desensitization of α4β2 and activation of α7 nicotinic acetylcholine receptors. We identify α7-dependent activation of upstream GABA neurons in the laterodorsal tegmentum (LDT) as a key regulator of heterogeneous DA release following aversive nicotine. Finally, inhibition of LDT GABA terminals in VTA prevents nicotine aversion. Together, our findings provide a mechanistic circuit-level understanding of nicotine's dose-dependent effects on reward and 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.