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Indeed, the medial prefrontal cortex (mPFC) projections to the nucleus accumbens (NAc) are critically important for reinstated cocaine\u2010seeking in a rodent model of cocaine relapse. This circuitry undergoes several epigenetic modifications following cocaine exposure, including changes in DNA methylation that are associated with drug\u2010seeking behavior. We have previously shown that methyl supplementation via L\u2010Methionine (MET) administration attenuates cocaine\u2010seeking behavior and reverses expression and methylation patterns of the immediate early gene <jats:italic>c\u2010fos<\/jats:italic>, suggesting that MET may act by altering the excitability of this circuitry during cocaine reinstatement. In the current study, male rats were microinjected with an adeno\u2010associated virus overexpressing halorhodopsin in the mPFC, optical fibers were surgically implanted into the NAc, and the rats were given injections of MET daily. Rats underwent acquisition of cocaine self\u2010administration (0.75 mg\/kg\/infusion, 2\u2010h sessions) followed by extinction training in the absence of drug\u2010paired cues. Two reinstatement tests were conducted: cue\u2010induced reinstatement without optogenetic manipulations and cocaine\u2010primed reinstatement with optogenetic inhibition of mPFC\u2010to\u2010NAc projections. There were no group differences before the cocaine\u2010primed reinstatement session, and all groups showed robust cue\u2010induced reinstatement. Both rats treated with MET and rats that received mPFC\u2010to\u2010NAc inhibition showed an abolishment of cocaine\u2010primed reinstatement, suggesting that systemic methyl supplementation may act through this critical circuity.<\/jats:p>","DOI":"10.1111\/1749-4877.12365","type":"journal-article","created":{"date-parts":[[2018,10,15]],"date-time":"2018-10-15T07:09:41Z","timestamp":1539587381000},"page":"795-803","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Optogenetic inhibition of medial prefrontal cortex projections to the nucleus accumbens core and methyl supplementation via L\u2010Methionine attenuates cocaine\u2010primed reinstatement"],"prefix":"10.1111","volume":"13","author":[{"given":"Katherine N.","family":"WRIGHT","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences and Program in Neuroscience Florida State University  Tallahassee Florida 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