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An interaction between locus coeruleus (LC) noradrenergic neurons and the posterior ventral tegmental area (pVTA) dopaminergic system, in the processing of drug\u2010triggered reward, has been suggested, but not demonstrated in behaving animals. Herein, we try to tease out the precise role of noradrenergic neurons in the LC\u2013VTA circuit in mediating reward and reinforcement behavior associated with ethanol. In the standard two\u2010lever (active\/inactive) operant paradigm, the rats were trained to self\u2010administer ethanol in pVTA and subjected to pharmacological intervention. Intra\u2010pVTA administration of phenylephrine (alpha\u20101 adrenoceptor agonist) increased ethanol self\u2010administration, while prazosin and disulfiram (agents that reduce noradrenergic tone) produced opposite effects. While degeneration [<jats:italic>N<\/jats:italic>\u2010(2\u2010chloroethyl)\u2010<jats:italic>N<\/jats:italic>\u2010ethyl\u20102\u2010bromobenzylamine hydrochloride, DSP\u20104, intraperitoneal route] or silencing (lidocaine or muscimol, both via intra\u2010LC route) of the LC noradrenergic neurons decreased, phenylephrine via the intra\u2010LC route reinstated ethanol self\u2010administration. Furthermore, lidocaine reduced ethanol self\u2010administration, but the effect was fully attenuated by noradrenaline given directly in the pVTA. This suggests that the feedback signals from LC to pVTA are necessary to sustain the ethanol self\u2010infusion activity. Ethanol self\u2010administration significantly increased tyrosine hydroxylase immunoreactivity in pVTA and LC; the response was blocked by DSP\u20104 pre\u2010treatment. While dopamine D<jats:sub>1<\/jats:sub>, but not D<jats:sub>2<\/jats:sub>, receptors were localized on noradrenergic LC neurons, pre\u2010treatment with SCH\u201023390 (intra\u2010LC) dampened the lever press activity. We suggest that two\u2010way communications between VTA and LC regions is essential for ethanol\u2010triggered reinforcement behavior.<\/jats:p>","DOI":"10.1111\/adb.12321","type":"journal-article","created":{"date-parts":[[2015,11,9]],"date-time":"2015-11-09T01:38:45Z","timestamp":1447033125000},"page":"291-302","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Noradrenergic inputs from locus coeruleus to posterior ventral tegmental area are essential to support ethanol reinforcement"],"prefix":"10.1111","volume":"22","author":[{"given":"Gajanan P.","family":"Shelkar","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences Rashtrasant Tukadoji Maharaj Nagpur University India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Santosh","family":"Kumar","sequence":"additional","affiliation":[{"name":"School of Biological Sciences National Institute of Science Education and Research (NISER) Institute of Physics Campus Sachivalaya Marg, PO Sainik School, Bhubaneswar India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Praful S.","family":"Singru","sequence":"additional","affiliation":[{"name":"School of Biological Sciences National Institute of Science Education and Research (NISER) Institute of Physics Campus Sachivalaya Marg, PO Sainik School, Bhubaneswar India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nishikant K.","family":"Subhedar","sequence":"additional","affiliation":[{"name":"Indian Institute of Science Education and Research (IISER) India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dadasaheb M.","family":"Kokare","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Rashtrasant Tukadoji Maharaj Nagpur University India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,11,8]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"76","article-title":"Noradrenergic mediation of the positive reinforcing properties of ethanol: II. 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