{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:35:09Z","timestamp":1791300909160,"version":"4.1.0"},"reference-count":50,"publisher":"Society for Neuroscience","issue":"45","license":[{"start":{"date-parts":[[2013,5,7]],"date-time":"2013-05-07T00:00:00Z","timestamp":1367884800000},"content-version":"vor","delay-in-days":181,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2012,11,7]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1523\/jneurosci.2846-12.2012","type":"journal-article","created":{"date-parts":[[2012,11,7]],"date-time":"2012-11-07T12:38:02Z","timestamp":1352291882000},"page":"15849-15858","source":"Crossref","is-referenced-by-count":39,"title":["The Small G Protein H-Ras in the Mesolimbic System Is a Molecular Gateway to Alcohol-Seeking and Excessive Drinking Behaviors"],"prefix":"10.1523","volume":"32","author":[{"given":"Sami","family":"Ben Hamida","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremie","family":"Neasta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy 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