ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
The small G protein H-Ras in the mesolimbic system is a molecular gateway to alcohol-seeking and excessive drinking behaviors.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 39 citations in OpenAlex.
- Alcohol effects on associative and sensorimotor cortico-thalamo-basal ganglia circuits alter decision making and alcohol intake.Alcohol (Fayetteville, N.Y.) · 2025Review
- Paradoxical mTORC1-Dependent microRNA-mediated Translation Repression in the Nucleus Accumbens of Male Mice Consuming Alcohol Attenuates Glycolysis.Nature communications · 2025Article
- Identifying a novel biological mechanism for alcohol addiction associated with circRNA networks acting as potential miRNA sponges.Addiction biology · 2021Article
- cAMP-Fyn signaling in the dorsomedial striatum direct pathway drives excessive alcohol use.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Article
- Article
- Mammalian target of rapamycin complex 1 and its downstream effector collapsin response mediator protein-2 drive reinstatement of alcohol reward seeking.Addiction biology · 2019Article
- The Inhibition of RasGRF2, But Not RasGRF1, Alters Cocaine Reward in Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- TrkB-dependent disinhibition of the nucleus accumbens is enhanced by ethanol.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2019Article
- mTORC2 in the dorsomedial striatum of mice contributes to alcohol-dependent F-Actin polymerization, structural modifications, and consumption.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Article
- Targeting the intracellular signaling "STOP" and "GO" pathways for the treatment of alcohol use disorders.Psychopharmacology · 2018Review
- Region specific activation of the AKT and mTORC1 pathway in response to excessive alcohol intake in rodents.Addiction biology · 2017Article
- Prosapip1-Dependent Synaptic Adaptations in the Nucleus Accumbens Drive Alcohol Intake, Seeking, and Reward.Neuron · 2017Article
- Genetic studies of alcohol dependence in the context of the addiction cycle.Neuropharmacology · 2017Review
- Promising pharmacogenetic targets for treating alcohol use disorder: evidence from preclinical models.Pharmacogenomics · 2017Review
- Orbitofrontal Neuroadaptations and Cross-Species Synaptic Biomarkers in Heavy-Drinking Macaques.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- mTORC1-dependent translation of collapsin response mediator protein-2 drives neuroadaptations underlying excessive alcohol-drinking behaviors.Molecular psychiatry · 2017Article
- Molecular mechanisms underlying alcohol-drinking behaviours.Nature reviews. Neuroscience · 2016Review
- Dependence-induced ethanol drinking and GABA neurotransmission are altered in Alk deficient mice.Neuropharmacology · 2016Article
- Chronic intermittent ethanol exposure and withdrawal leads to adaptations in nucleus accumbens core postsynaptic density proteome and dendritic spines.Addiction biology · 2016Article
- The First Alcohol Drink Triggers mTORC1-Dependent Synaptic Plasticity in Nucleus Accumbens Dopamine D1 Receptor Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Uncontrolled consumption of alcohol is a hallmark of alcohol abuse disorders; however, the central molecular mechanisms underlying excessive alcohol consumption are still unclear. Here, we report that the GTP binding protein, H-Ras in the nucleus accumbens (NAc) plays a key role in neuroadaptations that underlie excessive alcohol-drinking behaviors. Specifically, acute (15 min) systemic administration of alcohol (2.5 g/kg) leads to the activation of H-Ras in the NAc of mice, which is observed even 24 h later. Similarly, rat operant self-administration of alcohol (20%) also results in the activation of H-Ras in the NAc. Using the same procedures, we provide evidence suggesting that the exchange factor GRF1 is upstream of H-Ras activation by alcohol. Importantly, we show that infection of mice NAc with lentivirus expressing a short hairpin RNA that targets the H-Ras gene produces a significant reduction of voluntary consumption of 20% alcohol. In contrast, knockdown of H-Ras in the NAc of mice did not alter water, quinine, and saccharin intake. Furthermore, using two-bottle choice and operant self-administration procedures, we show that inhibiting H-Ras activity by intra-NAc infusion of the farnesyltransferase inhibitor, FTI-276, produced a robust decrease of rats' alcohol drinking; however, sucrose consumption was unaltered. Finally, intra-NAc infusion of FTI-276 also resulted in an attenuation of seeking for alcohol. Together, these results position H-Ras as a central molecular mediator of alcohol's actions within the mesolimbic system and put forward the potential value of the enzyme as a novel target to treat alcohol use disorders.
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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.