{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T17:35:36Z","timestamp":1780767336114,"version":"3.54.1"},"reference-count":49,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2020,8,1]],"date-time":"2020-08-01T00:00:00Z","timestamp":1596240000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,8,1]],"date-time":"2020-08-01T00:00:00Z","timestamp":1596240000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/100005984","name":"Dr. Miriam and Sheldon G. Adelson Medical Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005984","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Biochemistry and Behavior"],"published-print":{"date-parts":[[2020,8]]},"DOI":"10.1016\/j.pbb.2020.172954","type":"journal-article","created":{"date-parts":[[2020,5,26]],"date-time":"2020-05-26T11:23:34Z","timestamp":1590492214000},"page":"172954","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":7,"special_numbering":"C","title":["mTORC1 pathway is involved in the kappa opioid receptor activation-induced increase in excessive alcohol drinking in mice"],"prefix":"10.1016","volume":"195","author":[{"given":"Yan","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yupu","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Jeanne","family":"Kreek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.pbb.2020.172954_bb0005","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1111\/acer.13406","article-title":"Role of the dynorphin\/kappa opioid receptor system in the motivational effects of ethanol","volume":"41","author":"Anderson","year":"2017","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"10.1016\/j.pbb.2020.172954_bb0010","author":"Andrews"},{"key":"10.1016\/j.pbb.2020.172954_bb0015","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1523\/JNEUROSCI.2254-15.2016","article-title":"The first alcohol drink triggers mTORC1-dependent synaptic plasticity in nucleus accumbens dopamine D1 receptor neurons","volume":"36","author":"Beckley","year":"2016","journal-title":"J. Neurosci."},{"key":"10.1016\/j.pbb.2020.172954_bb0020","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate - a practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Stat. Soc. Ser. B Methodol."},{"key":"10.1016\/j.pbb.2020.172954_bb0025","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s00213-010-1806-y","article-title":"Kinase cascades and ligand-directed signaling at the kappa opioid receptor","volume":"210","author":"Bruchas","year":"2010","journal-title":"Psychopharmacology"},{"key":"10.1016\/j.pbb.2020.172954_bb0030","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/npp.2015.258","article-title":"Dynorphin, dysphoria, and dependence: the stress of addiction","volume":"41","author":"Chavkin","year":"2016","journal-title":"Neuropsychopharmacology"},{"key":"10.1016\/j.pbb.2020.172954_bb0035","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.neuropharm.2016.01.010","article-title":"Functional regulation of PI3K-associated signaling in the accumbens by binge alcohol drinking in male but not female mice","volume":"105","author":"Cozzoli","year":"2016","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.pbb.2020.172954_bb0040","doi-asserted-by":"crossref","first-page":"2774","DOI":"10.1016\/j.celrep.2016.02.069","article-title":"Dynorphin controls the gain of an amygdalar anxiety circuit","volume":"14","author":"Crowley","year":"2016","journal-title":"Cell Rep."},{"key":"10.1016\/j.pbb.2020.172954_bb0045","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1111\/j.1369-1600.2011.00326.x","article-title":"Different alcohol exposures induce selective alterations on the expression of dynorphin and nociceptin systems related genes in rat brain","volume":"13","author":"D\u2019Addario","year":"2013","journal-title":"Addict. Biol."},{"key":"10.1016\/j.pbb.2020.172954_bb0050","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"10.1016\/j.pbb.2020.172954_bb0055","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1038\/s41386-018-0015-y","article-title":"Preclinical evaluation of the kappa-opioid receptor antagonist CERC-501 as a candidate therapeutic for alcohol use disorders","volume":"43","author":"Domi","year":"2018","journal-title":"Neuropsychopharmacology"},{"key":"10.1016\/j.pbb.2020.172954_bb0060","doi-asserted-by":"crossref","first-page":"15523","DOI":"10.1523\/JNEUROSCI.2970-15.2015","article-title":"Glutamate receptors within the mesolimbic dopamine system mediate alcohol relapse behavior","volume":"35","author":"Eisenhardt","year":"2015","journal-title":"J. Neurosci."},{"key":"10.1016\/j.pbb.2020.172954_bb0065","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.neuropharm.2019.01.017","article-title":"Effect of chronic alcohol vapor exposure on reinstatement of alcohol seeking induced by U50,488","volume":"148","author":"Funk","year":"2019","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.pbb.2020.172954_bb0070","doi-asserted-by":"crossref","first-page":"19802","DOI":"10.1073\/pnas.1319700110","article-title":"RNA-sequencing from single nuclei","volume":"110","author":"Grindberg","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.pbb.2020.172954_bb0075","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1038\/s41386-019-0423-7","article-title":"Role of RGS12 in the differential regulation of kappa opioid receptor-dependent signaling and behavior","volume":"44","author":"Gross","year":"2019","journal-title":"Neuropsychopharmacology"},{"key":"10.1016\/j.pbb.2020.172954_bb0080","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s002130000601","article-title":"Kappa-opioid receptors and relapse-like drinking in long-term ethanol-experienced rats","volume":"153","author":"Holter","year":"2000","journal-title":"Psychopharmacology"},{"key":"10.1016\/j.pbb.2020.172954_bb0085","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1111\/j.1530-0277.2011.01545.x","article-title":"Persistent escalation of alcohol drinking in C57BL\/6J mice with intermittent access to 20% alcohol","volume":"35","author":"Hwa","year":"2011","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"10.1016\/j.pbb.2020.172954_bb0090","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1016\/j.biopsych.2013.03.014","article-title":"The one-two punch of alcoholism: role of central amygdala dynorphin\/kappa-opioid receptors","volume":"75","author":"Kissler","year":"2014","journal-title":"Biol. Psychiatry"},{"key":"10.1016\/j.pbb.2020.172954_bb0095","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1093\/ijnp\/pyx041","article-title":"Adolescent alcohol exposure-induced changes in alpha-melanocyte stimulating hormone and neuropeptide Y pathways via histone acetylation in the brain during adulthood","volume":"20","author":"Kokare","year":"2017","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"10.1016\/j.pbb.2020.172954_bb0100","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1176\/appi.ajp.2007.05030503","article-title":"Stress, dysregulation of drug reward pathways, and the transition to drug dependence","volume":"164","author":"Koob","year":"2007","journal-title":"Am. J. Psychiatry"},{"key":"10.1016\/j.pbb.2020.172954_bb0105","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1016\/j.biopsych.2019.05.021","article-title":"The kappa opioid receptor is associated with naltrexone-induced reduction of drinking and craving","volume":"86","author":"de Laat","year":"2019","journal-title":"Biol. Psychiatry"},{"key":"10.1016\/j.pbb.2020.172954_bb0110","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.1111\/adb.12464","article-title":"Region specific activation of the AKT and mTORC1 pathway in response to excessive alcohol intake in rodents","volume":"22","author":"Laguesse","year":"2017","journal-title":"Addict. Biol."},{"key":"10.1016\/j.pbb.2020.172954_bb0115","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.neuron.2017.08.037","article-title":"Prosapip1-dependent synaptic adaptations in the nucleus accumbens drive alcohol intake, seeking, and reward","volume":"96","author":"Laguesse","year":"2017","journal-title":"Neuron"},{"key":"10.1016\/j.pbb.2020.172954_bb0120","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1038\/s41386-018-0012-1","article-title":"mTORC2 in the dorsomedial striatum of mice contributes to alcohol-dependent F-actin polymerization, structural modifications, and consumption","volume":"43","author":"Laguesse","year":"2018","journal-title":"Neuropsychopharmacology"},{"key":"10.1016\/j.pbb.2020.172954_bb0130","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","article-title":"Feature counts: an efficient general-purpose program for assigning sequence reads to genomic features","volume":"30","author":"Liao","year":"2014","journal-title":"Bioinformatics"},{"key":"10.1016\/j.pbb.2020.172954_bb0135","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.physbeh.2007.05.039","article-title":"Ethanol alters the effect of kappa receptor ligands on dopamine release in the nucleus accumbens","volume":"92","author":"Lindholm","year":"2007","journal-title":"Physiol. Behav."},{"key":"10.1016\/j.pbb.2020.172954_bb0140","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1038\/s41386-018-0155-0","article-title":"Phosphoproteomic approach for agonist-specific signaling in mouse brains: mTOR pathway is involved in \u03ba opioid aversion","volume":"44","author":"Liu","year":"2019","journal-title":"Neuropsychopharmacology"},{"key":"10.1016\/j.pbb.2020.172954_bb0145","doi-asserted-by":"crossref","first-page":"2393","DOI":"10.1096\/fj.07-099135","article-title":"Dynorphin is a downstream effector of striatal BDNF regulation of ethanol intake","volume":"22","author":"Logrip","year":"2008","journal-title":"FASEB J."},{"key":"10.1016\/j.pbb.2020.172954_bb0150","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"10.1016\/j.pbb.2020.172954_bb0155","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/978-3-642-28720-6_143","article-title":"Synaptic effects induced by alcohol","volume":"13","author":"Lovinger","year":"2013","journal-title":"Curr. Top. Behav. Neurosci."},{"key":"10.1016\/j.pbb.2020.172954_bb0160","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1038\/nrm2672","article-title":"Molecular mechanisms of mTOR-mediated translational control","volume":"10","author":"Ma","year":"2009","journal-title":"Nat Rev Mol Cell Biol"},{"key":"10.1016\/j.pbb.2020.172954_bb0165","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.pbb.2014.12.007","article-title":"Gene expression changes in serotonin, GABA-A receptors, neuropeptides and ion channels in the dorsal raphe nucleus of adolescent alcohol-preferring rats following binge-like alcohol drinking","volume":"29","author":"McClintick","year":"2015","journal-title":"Pharmacol. Biochem. Behav."},{"key":"10.1016\/j.pbb.2020.172954_bb0170","doi-asserted-by":"crossref","first-page":"2537","DOI":"10.1111\/acer.13258","article-title":"Withdrawal from chronic nicotine exposure produces region-specific tolerance to alcohol-stimulated GluA1 phosphorylation","volume":"40","author":"McGinn","year":"2016","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"10.1016\/j.pbb.2020.172954_bb0175","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0049274","article-title":"Nuclear RNA sequencing of the mouse erythroid cell transcriptome","volume":"7","author":"Mitchell","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.pbb.2020.172954_bb0180","doi-asserted-by":"crossref","first-page":"20093","DOI":"10.1073\/pnas.1005554107","article-title":"Role for mammalian target of rapamycin complex 1 signaling in neuroadaptations underlying alcohol-related disorders","volume":"107","author":"Neasta","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.pbb.2020.172954_bb0185","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1111\/j.1369-1600.2012.00494.x","article-title":"Long-term ethanol effects on acute stress responses: modulation by dynorphin","volume":"18","author":"R\u00e1cz","year":"2013","journal-title":"Addict. Biol."},{"key":"10.1016\/j.pbb.2020.172954_bb0190","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.physbeh.2004.10.007","article-title":"Evaluation of a simple model of ethanol drinking to intoxication in C57BL\/6J mice","volume":"84","author":"Rhodes","year":"2005","journal-title":"Physiol. Behav."},{"key":"10.1016\/j.pbb.2020.172954_bb0195","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1007\/s00213-018-4882-z","article-title":"Targeting the intracellular signaling \u201cSTOP\u201d and \u201cGO\u201d pathways for the treatment of alcohol use disorders","volume":"235","author":"Ron","year":"2018","journal-title":"Psychopharmacology"},{"key":"10.1016\/j.pbb.2020.172954_bb0200","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/ijnp\/pyv127","article-title":"Supersensitive kappa opioid receptors promotes ethanol withdrawal-related behaviors and reduce dopamine signaling in the nucleus accumbens","volume":"19","author":"Rose","year":"2016","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"10.1016\/j.pbb.2020.172954_bb0205","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1111\/j.1471-4159.1990.tb04963.x","article-title":"The effects of opioid peptides on dopamine release in the nucleus accumbens: an in vivo microdialysis study","volume":"55","author":"Spanagel","year":"1990","journal-title":"J. Neurochem."},{"key":"10.1016\/j.pbb.2020.172954_bb0210","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/s00213-010-1844-5","article-title":"Endogenous kappa-opioid mediation of stress-induced potentiation of ethanol-conditioned place preference and self-administration","volume":"210","author":"Sperling","year":"2010","journal-title":"Psychopharmacology"},{"key":"10.1016\/j.pbb.2020.172954_bb0215","doi-asserted-by":"crossref","first-page":"3492","DOI":"10.1021\/acs.jproteome.9b00394","article-title":"Proteomic profile of a chronic binge ethanol exposure model","volume":"18","author":"Starski","year":"2019","journal-title":"J. Proteome Res."},{"key":"10.1016\/j.pbb.2020.172954_bb0220","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1038\/sj.npp.1301438","article-title":"Pharmacological evidence for a motivational role of kappa-opioid systems in ethanol dependence","volume":"33","author":"Walker","year":"2008","journal-title":"Neuropsychopharmacology"},{"key":"10.1016\/j.pbb.2020.172954_bb0225","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s002130100788","article-title":"Enadoline, a selective kappa opioid agonist: comparison with butorphanol and hydromorphone in humans","volume":"157","author":"Walsh","year":"2001","journal-title":"Psychopharmacology"},{"key":"10.1016\/j.pbb.2020.172954_bb0230","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1124\/jpet.117.245621","article-title":"Involvement of activated brain stress responsive systems in excessive and \u201crelapse\u201d alcohol drinking in rodent models: implications for therapeutics","volume":"366","author":"Zhou","year":"2018","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"10.1016\/j.pbb.2020.172954_bb0235","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1111\/acer.14033","article-title":"Combination of clinically utilized kappa opioid receptor agonist nalfurafine with low-dose naltrexone reduces excessive alcohol drinking in male and female mice","volume":"43","author":"Zhou","year":"2019","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"10.1016\/j.pbb.2020.172954_bb0240","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.regpep.2014.07.002","article-title":"Modulation of pro-opiomelanocortin gene expression by ethanol in mouse anterior pituitary corticotrope tumor cell AtT20","volume":"192","author":"Zhou","year":"2014","journal-title":"Regul. Pept."},{"key":"10.1016\/j.pbb.2020.172954_bb0245","doi-asserted-by":"crossref","first-page":"E131","DOI":"10.1111\/j.1530-0277.2012.01867.x","article-title":"Voluntary alcohol drinking enhances proopiomelanocortin (POMC) gene expression in nucleus accumbens shell and hypothalamus of Sardinian alcohol-preferring rats","volume":"37","author":"Zhou","year":"2013","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"10.1016\/j.pbb.2020.172954_bb0250","doi-asserted-by":"crossref","first-page":"e12600","DOI":"10.1111\/gbb.12600","article-title":"Nuclear transcriptional change in hypothalamus of Pomc enhancer knockout mice after excessive alcohol drinking","volume":"18","author":"Zhou","year":"2019","journal-title":"Genes Brain Behavior"}],"container-title":["Pharmacology Biochemistry and Behavior"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0091305720300538?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0091305720300538?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T04:38:09Z","timestamp":1758775089000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0091305720300538"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8]]},"references-count":49,"alternative-id":["S0091305720300538"],"URL":"https:\/\/doi.org\/10.1016\/j.pbb.2020.172954","relation":{},"ISSN":["0091-3057"],"issn-type":[{"value":"0091-3057","type":"print"}],"subject":[],"published":{"date-parts":[[2020,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"mTORC1 pathway is involved in the kappa opioid receptor activation-induced increase in excessive alcohol drinking in mice","name":"articletitle","label":"Article Title"},{"value":"Pharmacology Biochemistry and Behavior","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.pbb.2020.172954","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"172954"}}