ArticleNeuroscience2008
Ethanol dually modulates GABAergic synaptic transmission onto dopaminergic neurons in ventral tegmental area: role of mu-opioid receptors.
Article in Neuroscience, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.
- Classic psychedelics and alcohol use disorders: A systematic review of human and animal studies.Addiction biology · 2022Pooled it
- Review
- Nicotine engages a VTA-NAc feedback loop to inhibit amygdala-projecting dopamine neurons and induce anxiety-like behaviors.Nature communications · 2025Article
- Naltrexone Alters Neurochemical and Behavioral Parameters in a Zebrafish Model of Repeated Alcohol Exposure.Neurochemical research · 2025Article
- Effects of chronic voluntary alcohol consumption on PDE10A availability: a longitudinal behavioral and [European journal of nuclear medicine and molecular imaging · 2022Article
- Opioid Receptor-Mediated Regulation of Neurotransmission in the Brain.Frontiers in molecular neuroscience · 2022Review
- The Significance of Toll-Like Receptors in the Neuroimmunologic Background of Alcohol Dependence.Frontiers in psychiatry · 2021Review
- Dose-dependent induction of CPP or CPA by intra-pVTA ethanol: Role of mu opioid receptors and effects on NMDA receptors.Progress in neuro-psychopharmacology & biological psychiatry · 2020Article
- Neural Mechanisms Underlying the Rewarding and Therapeutic Effects of Ketamine as a Treatment for Alcohol Use Disorder.Frontiers in behavioral neuroscience · 2020Article
- An Assessment between D1 Receptor Agonist and D2 receptor Antagonist into the Ventral Tegmental Area on Conditioned Place Preference and Locomotor Activity.Advanced biomedical research · 2019Article
- Inhibition of Morphine- and Ethanol-Mediated Stimulation of Mesolimbic Dopamine Neurons byFrontiers in neuroscience · 2019Article
- Histone Deacetylase Inhibitor Suberanilohydroxamic Acid Treatment Reverses Hyposensitivity to γ-Aminobutyric Acid in the Ventral Tegmental Area During Ethanol Withdrawal.Alcoholism, clinical and experimental research · 2018Article
- The dynamic interaction between pain and opioid misuse.British journal of pharmacology · 2018Review
- Ethanol actions on the ventral tegmental area: novel potential targets on reward pathway neurons.Psychopharmacology · 2018Review
- Acute ethanol modulation of neurocircuit function in the nucleus of the tractus solitarius.Brain research bulletin · 2018Article
- Convergent Neuronal Plasticity and Metaplasticity Mechanisms of Stress, Nicotine, and Alcohol.Annual review of pharmacology and toxicology · 2018Review
- Sex and β-Endorphin Influence the Effects of Ethanol on LimbicFrontiers in genetics · 2018Article
- Review
- Effects of acute alcohol on excitability in the CNS.Neuropharmacology · 2017Review
- Effects of acute alcohol ingestion on eye movements and cognition: A double-blind, placebo-controlled study.PloS one · 2017Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The mesolimbic dopaminergic system, originating from the ventral tegmental area (VTA) is implicated in the rewarding properties of ethanol. VTA dopaminergic neurons are under the tonic control of GABAergic innervations. Application of GABAergic agents changes ethanol consumption. However, it is unclear how acute ethanol modulates GABAergic inputs to dopaminergic neurons in the VTA. This report describes ethanol at clinically relevant concentrations (10-40 mM) dually modulates inhibitory postsynaptic currents (IPSCs). IPSCs were mediated by GABA(A) receptors and were recorded from VTA dopaminergic neurons in acute midbrain slices of rats. Acute application of ethanol reduced the amplitude and increased the paired pulse ratio of evoked IPSCs. Ethanol lowered the frequency but not the amplitude of spontaneous IPSCs. Nevertheless, ethanol had no effect on miniature IPSCs recorded in the presence of tetrodotoxin. These data indicate that ethanol inhibits GABAergic synaptic transmission to dopaminergic neurons by presynaptic mechanisms, and that ethanol inhibition depends on the firing of GABAergic neurons. Application of CGP 52432, a GABA(B) receptor antagonist, did not change ethanol inhibition of IPSCs. Tyr-d-Ala-Gly-N-Me-Phe-Gly-ol enkephalin (DAMGO), a mu-opioid receptor agonist, conversely, silenced VTA GABAergic neurons and inhibited IPSCs. Of note, in the presence of a saturating concentration of DAMGO (3 microM), ethanol potentiated the remaining IPSCs. Thus, ethanol dually modulates GABAergic transmission to dopaminergic neurons in the VTA. Ethanol modulation depends on the activity of VTA GABAergic neurons, which were inhibited by the activation of mu-opioid receptors. This dual modulation of GABAergic transmission by ethanol may be an important mechanism underlying alcohol addiction.
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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.