{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,14]],"date-time":"2025-06-14T22:25:22Z","timestamp":1749939922326},"reference-count":41,"publisher":"Wiley","issue":"s1","license":[{"start":{"date-parts":[[2012,7,23]],"date-time":"2012-07-23T00:00:00Z","timestamp":1343001600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Alcoholism Clin &amp; Exp Res"],"published-print":{"date-parts":[[2013,1]]},"abstract":"Background<\/jats:title>Alcoholism is a neuroadaptive disorder, and the understanding of the mechanisms of the high rates of relapse, which characterize it, represents one of the most demanding challenges in alcoholism and addiction research. The extracellular signal\u2013regulated kinase (ERK<\/jats:styled-content>) is an intracellular kinase, critical for neuroplasticity in the adult brain that is suggested to play a fundamental role in the molecular mechanisms underlying drug addiction and relapse. We previously observed that a nonessential amino acid, l<\/jats:sc>\u2010cysteine, significantly decreases oral ethanol (E<\/jats:styled-content>tOH<\/jats:styled-content>) self\u2010administration, reinstatement of E<\/jats:styled-content>tOH<\/jats:styled-content>\u2010drinking behavior, and E<\/jats:styled-content>tOH<\/jats:styled-content> self\u2010administration break point.<\/jats:p><\/jats:sec>Methods<\/jats:title>Here, we tested whether l<\/jats:sc>\u2010cysteine can affect the ability of E<\/jats:styled-content>tOH<\/jats:styled-content> priming to induce reinstatement of E<\/jats:styled-content>tOH<\/jats:styled-content>\u2010seeking behavior. In addition, we determined the ability of E<\/jats:styled-content>tOH<\/jats:styled-content> priming to induce ERK<\/jats:styled-content> phosphorylation as well as the ability of l<\/jats:sc>\u2010cysteine to affect reinstatement\u2010elicited ERK<\/jats:styled-content> activation. To these purposes, Wistar rats were trained to nose\u2010poke for a 10% v\/v E<\/jats:styled-content>tOH<\/jats:styled-content> solution. After stable drug\u2010taking behavior was obtained, nose\u2010poking for E<\/jats:styled-content>tOH<\/jats:styled-content> was extinguished, and reinstatement of drug seeking, as well as reinstatement\u2010elicited pERK<\/jats:styled-content>, was determined after an oral, noncontingent, priming of E<\/jats:styled-content>tOH<\/jats:styled-content> (0.08\u00a0g\/kg). Rats were pretreated with either saline or l<\/jats:sc>\u2010cysteine (80 to 120\u00a0mg\/kg) 30\u00a0minutes before testing for reinstatement.<\/jats:p><\/jats:sec>Results<\/jats:title>The findings of this study confirm that the noncontingent delivery of a nonpharmacologically active dose of E<\/jats:styled-content>tOH<\/jats:styled-content> to rats, whose previous self\u2010administration behavior had been extinguished, results in significant reinstatement into E<\/jats:styled-content>tOH<\/jats:styled-content>\u2010seeking behavior. In addition, the results indicate that reinstatement selectively activates ERK<\/jats:styled-content> phosphorylation in the shell of the nucleus accumbens (A<\/jats:styled-content>cb) and that pretreatment with l<\/jats:sc>\u2010cysteine reduces either reinstatement of E<\/jats:styled-content>tOH<\/jats:styled-content> seeking and reinstatement\u2010elicited pERK<\/jats:styled-content> in the A<\/jats:styled-content>cbS<\/jats:styled-content>h.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Altogether, these results indicate that l<\/jats:sc>\u2010cysteine could be an effective pharmacological agent for the prevention of behavioral and molecular correlates of E<\/jats:styled-content>tOH<\/jats:styled-content>\u2010primed reinstatement of E<\/jats:styled-content>tOH<\/jats:styled-content> seeking and that the shell of the A<\/jats:styled-content>cb represents a critical neural substrate for priming\u2010elicited reinstatement mechanisms involving ERK<\/jats:styled-content> phosphorylation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1530-0277.2012.01877.x","type":"journal-article","created":{"date-parts":[[2012,7,23]],"date-time":"2012-07-23T14:07:17Z","timestamp":1343052437000},"source":"Crossref","is-referenced-by-count":14,"title":["Effects of l<\/scp>\u2010Cysteine on Reinstatement of Ethanol\u2010Seeking Behavior and on Reinstatement\u2010Elicited Extracellular Signal\u2013Regulated Kinase Phosphorylation in the Rat Nucleus Accumbens Shell"],"prefix":"10.1111","volume":"37","author":[{"given":"Alessandra T.","family":"Peana","sequence":"first","affiliation":[{"name":"Laboratory of Cognitive Neuroscience Department of Chemistry and Pharmacy University of Sassari Sassari Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Giugliano","sequence":"additional","affiliation":[{"name":"Department of Toxicology University of Cagliari Cagliari 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