{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T18:23:00Z","timestamp":1793211780399,"version":"4.5.0"},"reference-count":65,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2018,7,20]],"date-time":"2018-07-20T00:00:00Z","timestamp":1532044800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neuropsychopharmacol."],"published-print":{"date-parts":[[2019,4]]},"DOI":"10.1038\/s41386-018-0155-0","type":"journal-article","created":{"date-parts":[[2018,7,20]],"date-time":"2018-07-20T09:16:36Z","timestamp":1532078196000},"page":"939-949","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":95,"title":["Phosphoproteomic approach for agonist-specific signaling in mouse brains: mTOR pathway is involved in \u03ba opioid aversion"],"prefix":"10.1038","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2898-1667","authenticated-orcid":false,"given":"Jeffrey J.","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Ting","family":"Chiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly M.","family":"DiMattio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chongguang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor A.","family":"Gentile","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W.","family":"Muschamp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Cowan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Mann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee-Yuan","family":"Liu-Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,7,20]]},"reference":[{"key":"155_CR1","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1007\/978-3-662-44605-8_16","volume":"226","author":"A Cowan","year":"2015","unstructured":"Cowan A, Kehner GB, Inan S. Targeting Itch with ligands selective for kappa opioid receptors. Handb Exp Pharmacol. 2015;226:291\u2013314.","journal-title":"Handb Exp Pharmacol"},{"key":"155_CR2","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1124\/jpet.106.101998","volume":"318","author":"MA Ansonoff","year":"2006","unstructured":"Ansonoff MA, Zhang J, Czyzyk T, Rothman RB, Stewart J, Xu H, et al. Antinociceptive and hypothermic effects of Salvinorin A are abolished in a novel strain of kappa-opioid receptor-1 knockout mice. J Pharmacol Exp Ther. 2006;318:641\u20138.","journal-title":"J Pharmacol Exp Ther"},{"key":"155_CR3","doi-asserted-by":"crossref","unstructured":"Lemos JC, Chavkin C. Kappa opioid receptor function. In: Pasternak GW editors. The opiate receptors, 2nd ed. Humana Press; 2011. p. 265\u2013306.","DOI":"10.1007\/978-1-60761-993-2_11"},{"key":"155_CR4","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1126\/science.3016896","volume":"233","author":"A Pfeiffer","year":"1986","unstructured":"Pfeiffer A, Brantl V, Herz A, Emrich HM. Psychotomimesis mediated by kappa opiate receptors. Science. 1986;233:774\u20136.","journal-title":"Science"},{"key":"155_CR5","doi-asserted-by":"publisher","first-page":"11934","DOI":"10.1073\/pnas.182234399","volume":"99","author":"BL Roth","year":"2002","unstructured":"Roth BL, Baner K, Westkaemper R, Siebert D, Rice KC, Steinberg S, et al. Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist. Proc Natl Acad Sci USA. 2002;99:11934\u20139.","journal-title":"Proc Natl Acad Sci USA"},{"key":"155_CR6","doi-asserted-by":"publisher","first-page":"886","DOI":"10.1093\/emboj\/17.4.886","volume":"17","author":"F Simonin","year":"1998","unstructured":"Simonin F, Valverde O, Smadja C, Slowe S, Kitchen I, Dierich A, et al. Disruption of the kappa-opioid receptor gene in mice enhances sensitivity to chemical visceral pain, impairs pharmacological actions of the selective kappa-agonist U-50,488H and attenuates morphine withdrawal. EMBO J. 1998;17:886\u201397.","journal-title":"EMBO J"},{"key":"155_CR7","unstructured":"Yaksh TL, Wallace MS. Opioids, analgesia, and pain management. In: Brunton LL, Chabner BA, Knollmann BC, editors. Goodman & Gilman\u2019s the pharmacological basis of therapeutics. 12th ed. McGraw-Hill Co., Inc; 2011."},{"key":"155_CR8","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1097\/00002826-199619050-00009","volume":"19","author":"AC Pande","year":"1996","unstructured":"Pande AC, Pyke RE, Greiner M, Wideman GL, Benjamin R, Pierce MW. Analgesic efficacy of enadoline versus placebo or morphine in postsurgical pain. Clin Neuropharmacol. 1996;19:451\u20136.","journal-title":"Clin Neuropharmacol"},{"key":"155_CR9","doi-asserted-by":"publisher","first-page":"9","DOI":"10.2147\/IJNRD.S145720","volume":"11","author":"H Kozono","year":"2018","unstructured":"Kozono H, Yoshitani H, Nakano R. Post-marketing surveillance study of the safety and efficacy of nalfurafine hydrochloride (Remitch((R)) capsules 2.5 mug) in 3,762 hemodialysis patients with intractable pruritus. Int J Nephrol Renov Dis. 2018;11:9\u201324.","journal-title":"Int J Nephrol Renov Dis"},{"key":"155_CR10","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1159\/000341268","volume":"36","author":"H Kumagai","year":"2012","unstructured":"Kumagai H, Ebata T, Takamori K, Miyasato K, Muramatsu T, Nakamoto H, et al. Efficacy and safety of a novel k-agonist for managing intractable pruritus in dialysis patients. Am J Nephrol. 2012;36:175\u201383.","journal-title":"Am J Nephrol"},{"key":"155_CR11","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.1093\/ndt\/gfp588","volume":"25","author":"H Kumagai","year":"2010","unstructured":"Kumagai H, Ebata T, Takamori K, Muramatsu T, Nakamoto H, Suzuki H. Effect of a novel kappa-receptor agonist, nalfurafine hydrochloride, on severe itch in 337 haemodialysis patients: a Phase III, randomized, double-blind, placebo-controlled study. Nephrol Dial Transplant. 2010;25:1251\u20137.","journal-title":"Nephrol Dial Transplant"},{"key":"155_CR12","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1358\/dot.2009.45.5.1377595","volume":"45","author":"K Nakao","year":"2009","unstructured":"Nakao K, Mochizuki H. Nalfurafine hydrochloride: a new drug for the treatment of uremic pruritus in hemodialysis patients. Drugs Today. 2009;45:323\u20139.","journal-title":"Drugs Today"},{"key":"155_CR13","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/S0022-3565(25)33422-1","volume":"224","author":"PF Voigtlander von","year":"1983","unstructured":"von Voigtlander PF, Lahti RA, Ludens JH. U-50,488: a selective and structurally novel non-Mu (kappa) opioid agonist. J Pharmacol Exp Ther. 1983;224:7\u201312.","journal-title":"J Pharmacol Exp Ther"},{"key":"155_CR14","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1124\/jpet.107.132142","volume":"324","author":"Y Wang","year":"2008","unstructured":"Wang Y, Chen Y, Xu W, Lee DY, Ma Z, Rawls SM, et al. 2-Methoxymethyl-salvinorin B is a potent kappa opioid receptor agonist with longer lasting action in vivo than salvinorin A. J Pharmacol Exp Ther. 2008;324:1073\u201383.","journal-title":"J Pharmacol Exp Ther"},{"key":"155_CR15","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1124\/mol.115.099630","volume":"88","author":"LM Luttrell","year":"2015","unstructured":"Luttrell LM, Maudsley S, Bohn LM. Fulfilling the promise of \u201cbiased\u201d G protein-coupled receptor agonism. Mol Pharmacol. 2015;88:579\u201388.","journal-title":"Mol Pharmacol"},{"key":"155_CR16","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.bmcl.2015.12.024","volume":"26","author":"Z Rankovic","year":"2016","unstructured":"Rankovic Z, Brust TF, Bohn LM. Biased agonism: an emerging paradigm in GPCR drug discovery. Bioorg Med Chem Lett. 2016;26:241\u201350.","journal-title":"Bioorg Med Chem Lett"},{"key":"155_CR17","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1124\/jpet.114.216820","volume":"352","author":"KL White","year":"2015","unstructured":"White KL, Robinson JE, Zhu H, DiBerto JF, Polepally PR, Zjawiony JK, et al. The G protein-biased kappa-opioid receptor agonist RB-64 Is analgesic with a unique spectrum of activities in vivo. J Pharmacol Exp Ther. 2015;352:98\u2013109.","journal-title":"J Pharmacol Exp Ther"},{"key":"155_CR18","doi-asserted-by":"publisher","first-page":"12917","DOI":"10.1523\/JNEUROSCI.2444-15.2015","volume":"35","author":"JM Ehrich","year":"2015","unstructured":"Ehrich JM, Messinger DI, Knakal CR, Kuhar JR, Schattauer SS, Bruchas MR, et al. Kappa opioid receptor-induced aversion requires p38 MAPK Aactivation in VTA dopamine neurons. J Neurosci. 2015;35:12917\u201331.","journal-title":"J Neurosci"},{"key":"155_CR19","doi-asserted-by":"publisher","first-page":"11614","DOI":"10.1523\/JNEUROSCI.3769-07.2007","volume":"27","author":"MR Bruchas","year":"2007","unstructured":"Bruchas MR, Land BB, Aita M, Xu M, Barot SK, Li S, et al. Stress-induced p38 mitogen-activated protein kinase activation mediates kappa-opioid-dependent dysphoria. J Neurosci. 2007;27:11614\u201323.","journal-title":"J Neurosci"},{"key":"155_CR20","doi-asserted-by":"publisher","first-page":"18081","DOI":"10.1074\/jbc.M513640200","volume":"281","author":"MR Bruchas","year":"2006","unstructured":"Bruchas MR, Macey TA, Lowe JD, Chavkin C. Kappa opioid receptor activation of p38 MAPK is GRK3- and arrestin-dependent in neurons and astrocytes. J Biol Chem. 2006;281:18081\u20139.","journal-title":"J Biol Chem"},{"key":"155_CR21","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1016\/j.neuron.2011.06.011","volume":"71","author":"MR Bruchas","year":"2011","unstructured":"Bruchas MR, Schindler AG, Shankar H, Messinger DI, Miyatake M, Land BB, et al. Selective p38alpha MAPK deletion in serotonergic neurons produces stress resilience in models of depression and addiction. Neuron. 2011;71:498\u2013511.","journal-title":"Neuron"},{"key":"155_CR22","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.ceb.2013.11.010","volume":"27","author":"L Zhou","year":"2014","unstructured":"Zhou L, Bohn LM. Functional selectivity of GPCR signaling in animals. Curr Opin Cell Biol. 2014;27:102\u20138.","journal-title":"Curr Opin Cell Biol"},{"key":"155_CR23","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1038\/nature19949","volume":"537","author":"R Aebersold","year":"2016","unstructured":"Aebersold R, Mann M. Mass-spectrometric exploration of proteome structure and function. Nature. 2016;537:347\u201355.","journal-title":"Nature"},{"key":"155_CR24","doi-asserted-by":"publisher","first-page":"990","DOI":"10.1038\/nbt.3327","volume":"33","author":"SJ Humphrey","year":"2015","unstructured":"Humphrey SJ, Azimifar SB, Mann M. High-throughput phosphoproteomics reveals in vivo insulin signaling dynamics. Nat Biotechnol. 2015;33:990\u20135.","journal-title":"Nat Biotechnol"},{"key":"155_CR25","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1021\/acs.analchem.5b04123","volume":"88","author":"NM Riley","year":"2016","unstructured":"Riley NM, Coon JJ. Phosphoproteomics in the age of rapid and deep proteome profiling. Anal Chem. 2016;88:74\u201394.","journal-title":"Anal Chem"},{"key":"155_CR26","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1038\/383819a0","volume":"383","author":"HW Matthes","year":"1996","unstructured":"Matthes HW, Maldonado R, Simonin F, Valverde O, Slowe S, Kitchen I, et al. Loss of morphine-induced analgesia, reward effect and withdrawal symptoms in mice lacking the mu-opioid-receptor gene. Nature. 1996;383:819\u201323.","journal-title":"Nature"},{"key":"155_CR27","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1124\/jpet.104.073668","volume":"312","author":"Y Wang","year":"2005","unstructured":"Wang Y, Tang K, Inan S, Siebert D, Holzgrabe U, Lee DY, et al. Comparison of pharmacological activities of three distinct k ligands (Salvinorin A, TRK-820 and 3FLB) on k opioid receptors in vitro and their antipruritic and antinociceptive activities in vivo. J Pharmacol Exp Ther. 2005;312:220\u201330.","journal-title":"J Pharmacol Exp Ther"},{"key":"155_CR28","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/0160-5402(88)90078-2","volume":"20","author":"CW Murray","year":"1988","unstructured":"Murray CW, Porreca F, Cowan A. Methodological refinements to the mouse paw formalin test. An animal model of tonic pain. J Pharmacol Methods. 1988;20:175\u201386.","journal-title":"J Pharmacol Methods"},{"key":"155_CR29","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1016\/j.drugalcdep.2013.08.021","volume":"133","author":"W Xu","year":"2013","unstructured":"Xu W, Wang Y, Ma Z, Chiu YT, Huang P, Rasakham K, et al. l-Isocorypalmine reduces behavioral sensitization and rewarding effects of cocaine in mice by acting on dopamine receptors. Drug Alcohol Depend. 2013;133:693\u2013703.","journal-title":"Drug Alcohol Depend"},{"key":"155_CR30","unstructured":"Muschamp JW, Van't Veer A, Parsegian A, Gallo MS, Chen M, Neve RL, et al(2011). Activation of CREB in the nucleus accumbens shell produces anhedonia and resistance to extinction of fear in rats. J Neurosci. 31: 3095-103."},{"key":"155_CR31","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1038\/nbt.1511","volume":"26","author":"J Cox","year":"2008","unstructured":"Cox J, Mann M. MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat Biotechnol. 2008;26:1367\u201372.","journal-title":"Nat Biotechnol"},{"key":"155_CR32","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1038\/nmeth.3901","volume":"13","author":"S Tyanova","year":"2016","unstructured":"Tyanova S, Temu T, Sinitcyn P, Carlson A, Hein MY, Geiger T, et al. The Perseus computational platform for comprehensive analysis of (prote)omics data. Nat Methods. 2016;13:731\u201340.","journal-title":"Nat Methods"},{"key":"155_CR33","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-13-S16-S12","volume":"13","author":"J Cox","year":"2012","unstructured":"Cox J, Mann M. 1D and 2D annotation enrichment: a statistical method integrating quantitative proteomics with complementary high-throughput data. BMC Bioinform. 2012;13:S12.","journal-title":"BMC Bioinform"},{"key":"155_CR34","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.cmet.2016.10.004","volume":"25","author":"MS Robles","year":"2017","unstructured":"Robles MS, Humphrey SJ, Mann M. Phosphorylation is a central mechanism for Circadian control of metabolism and physiology. Cell Metab. 2017;25:118\u201327.","journal-title":"Cell Metab"},{"key":"155_CR35","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13250","volume":"7","author":"F Sacco","year":"2016","unstructured":"Sacco F, Humphrey SJ, Cox J, Mischnik M, Schulte A, Klabunde T, et al. Glucose-regulated and drug-perturbed phosphoproteome reveals molecular mechanisms controlling insulin secretion. Nat Commun. 2016;7:13250.","journal-title":"Nat Commun"},{"key":"155_CR36","doi-asserted-by":"publisher","first-page":"1819","DOI":"10.1038\/nn.4160","volume":"18","author":"K Sharma","year":"2015","unstructured":"Sharma K, Schmitt S, Bergner CG, Tyanova S, Kannaiyan N, Manrique-Hoyos N, et al. Cell type- and brain region-resolved mouse brain proteome. Nat Neurosci. 2015;18:1819\u201331.","journal-title":"Nat Neurosci"},{"key":"155_CR37","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1042\/BJ20141471","volume":"473","author":"C Chen","year":"2016","unstructured":"Chen C, Chiu YT, Wu W, Huang P, Mann A, Schulz S, et al. Determination of sites of U50,488H-promoted phosphorylation of the mouse kappa opioid receptor (KOPR): disconnect between KOPR phosphorylation and internalization. Biochem J. 2016;473:497\u2013508.","journal-title":"Biochem J"},{"key":"155_CR38","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/S0014-2999(99)00369-6","volume":"376","author":"T Seki","year":"1999","unstructured":"Seki T, Awamura S, Kimura C, Ide S, Sakano K, Minami M, et al. Pharmacological properties of TRK-820 on cloned mu-, delta- and kappa-opioid receptors and nociceptin receptor. Eur J Pharmacol. 1999;376:159\u201367.","journal-title":"Eur J Pharmacol"},{"key":"155_CR39","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1007\/s00213-003-1680-y","volume":"172","author":"MS Todtenkopf","year":"2004","unstructured":"Todtenkopf MS, Marcus JF, Portoghese PS, Carlezon WA Jr. Effects of kappa-opioid receptor ligands on intracranial self-stimulation in rats. Psychopharmacology. 2004;172:463\u201370.","journal-title":"Psychopharmacology"},{"key":"155_CR40","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1016\/0166-2236(88)90093-8","volume":"11","author":"A Mansour","year":"1988","unstructured":"Mansour A, Khachaturian H, Lewis ME, Akil H, Watson SJ. Anatomy of CNS opioid receptors. Trends Neurosci. 1988;11:308\u201314.","journal-title":"Trends Neurosci"},{"key":"155_CR41","doi-asserted-by":"publisher","first-page":"M111 014050","DOI":"10.1074\/mcp.M111.014050","volume":"11","author":"T Geiger","year":"2012","unstructured":"Geiger T, Wehner A, Schaab C, Cox J, Mann M. Comparative proteomic analysis of eleven common cell lines reveals ubiquitous but varying expression of most proteins. Mol Cell Proteom. 2012;11:M111 014050.","journal-title":"Mol Cell Proteom"},{"key":"155_CR42","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1038\/nbt0307-285","volume":"25","author":"R Amanchy","year":"2007","unstructured":"Amanchy R, Periaswamy B, Mathivanan S, Reddy R, Tattikota SG, Pandey A. A curated compendium of phosphorylation motifs. Nat Biotechnol. 2007;25:285\u20136.","journal-title":"Nat Biotechnol"},{"key":"155_CR43","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1038\/msb.2013.12","volume":"9","author":"RH Newman","year":"2013","unstructured":"Newman RH, Hu J, Rho HS, Xie Z, Woodard C, Neiswinger J, et al. Construction of human activity-based phosphorylation networks. Mol Syst Biol. 2013;9:655.","journal-title":"Mol Syst Biol"},{"key":"155_CR44","doi-asserted-by":"publisher","first-page":"9666","DOI":"10.1073\/pnas.171301998","volume":"98","author":"H Harada","year":"2001","unstructured":"Harada H, Andersen JS, Mann M, Terada N, Korsmeyer SJ. p70S6 kinase signals cell survival as well as growth, inactivating the pro-apoptotic molecule BAD. Proc Natl Acad Sci USA. 2001;98:9666\u201370.","journal-title":"Proc Natl Acad Sci USA"},{"key":"155_CR45","doi-asserted-by":"publisher","first-page":"27734","DOI":"10.1074\/jbc.M109.008177","volume":"284","author":"T Morita","year":"2009","unstructured":"Morita T, Sobue K. Specification of neuronal polarity regulated by local translation of CRMP2 and Tau via the mTOR-p70S6K pathway. J Biol Chem. 2009;284:27734\u201345.","journal-title":"J Biol Chem"},{"key":"155_CR46","doi-asserted-by":"publisher","first-page":"75","DOI":"10.3389\/fnmol.2015.00075","volume":"8","author":"A Biever","year":"2015","unstructured":"Biever A, Valjent E, Puighermanal E. Ribosomal protein S6 phosphorylation in the nervous system: from regulation to function. Front Mol Neurosci. 2015;8:75.","journal-title":"Front Mol Neurosci"},{"key":"155_CR47","doi-asserted-by":"publisher","first-page":"1774","DOI":"10.1016\/j.pnpbp.2011.05.010","volume":"35","author":"CS Jernigan","year":"2011","unstructured":"Jernigan CS, Goswami DB, Austin MC, Iyo AH, Chandran A, Stockmeier CA, et al. The mTOR signaling pathway in the prefrontal cortex is compromised in major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35:1774\u20139.","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"155_CR48","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1126\/science.1190287","volume":"329","author":"N Li","year":"2010","unstructured":"Li N, Lee B, Liu RJ, Banasr M, Dwyer JM, Iwata M, et al. mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science. 2010;329:959\u201364.","journal-title":"Science"},{"key":"155_CR49","doi-asserted-by":"publisher","first-page":"5422","DOI":"10.1523\/JNEUROSCI.0955-08.2008","volume":"28","author":"L Meikle","year":"2008","unstructured":"Meikle L, Pollizzi K, Egnor A, Kramvis I, Lane H, Sahin M, et al. Response of a neuronal model of tuberous sclerosis to mammalian target of rapamycin (mTOR) inhibitors: effects on mTORC1 and Akt signaling lead to improved survival and function. J Neurosci. 2008;28:5422\u201332.","journal-title":"J Neurosci"},{"key":"155_CR50","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.nlm.2007.12.004","volume":"90","author":"J Blundell","year":"2008","unstructured":"Blundell J, Kouser M, Powell CM. Systemic inhibition of mammalian target of rapamycin inhibits fear memory reconsolidation. Neurobiol Learn Mem. 2008;90:28\u201335.","journal-title":"Neurobiol Learn Mem"},{"key":"155_CR51","doi-asserted-by":"publisher","first-page":"1685","DOI":"10.1016\/S0024-3205(99)00417-8","volume":"65","author":"T Endoh","year":"1999","unstructured":"Endoh T, Matsuura H, Tajima A, Izumimoto N, Tajima C, Suzuki T, et al. Potent antinociceptive effects of TRK-820, a novel kappa-opioid receptor agonist. Life Sci. 1999;65:1685\u201394.","journal-title":"Life Sci"},{"key":"155_CR52","doi-asserted-by":"publisher","first-page":"1717","DOI":"10.1016\/S0024-3205(01)00957-2","volume":"68","author":"M Tsuji","year":"2001","unstructured":"Tsuji M, Takeda H, Matsumiya T, Nagase H, Narita M, Suzuki T. The novel kappa-opioid receptor agonist TRK-820 suppresses the rewarding and locomotor-enhancing effects of morphine in mice. Life Sci. 2001;68:1717\u201325.","journal-title":"Life Sci"},{"key":"155_CR53","unstructured":"Lazenka ML, Moerke MJ, Townsend EA, Freeman KB, Carroll FI, Negus SS (2018). Dissociable effects of the kappa opioid receptor agonist nalfurafine on pain\/itch-stimulated and pain\/itch-depressed behaviors in male rats. Psychopharmacology (Berl) 2018; 235: 203-213."},{"key":"155_CR54","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1124\/jpet.108.143925","volume":"328","author":"MC Ko","year":"2009","unstructured":"Ko MC, Husbands SM. Effects of atypical kappa-opioid receptor agonists on intrathecal morphine-induced itch and analgesia in primates. J Pharmacol Exp Ther. 2009;328:193\u2013200.","journal-title":"J Pharmacol Exp Ther"},{"key":"155_CR55","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.ejphar.2003.08.007","volume":"477","author":"H Umeuchi","year":"2003","unstructured":"Umeuchi H, Togashi Y, Honda T, Nakao K, Okano K, Tanaka T, et al. Involvement of central mu-opioid system in the scratching behavior in mice, and the suppression of it by the activation of kappa-opioid system. Eur J Pharmacol. 2003;477:29\u201335.","journal-title":"Eur J Pharmacol"},{"key":"155_CR56","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/S0014-2999(99)00815-8","volume":"387","author":"T Endoh","year":"2000","unstructured":"Endoh T, Tajima A, Suzuki T, Kamei J, Narita M, Tseng L, et al. Characterization of the antinociceptive effects of TRK-820 in the rat. Eur J Pharmacol. 2000;387:133\u201340.","journal-title":"Eur J Pharmacol"},{"key":"155_CR57","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1016\/j.peptides.2010.11.022","volume":"32","author":"S Inan","year":"2011","unstructured":"Inan S, Dun NJ, Cowan A. Investigation of gastrin-releasing peptide as a mediator for 5\u2019-guanidinonaltrindole-induced compulsive scratching in mice. Peptides. 2011;32:286\u201392.","journal-title":"Peptides"},{"key":"155_CR58","doi-asserted-by":"publisher","first-page":"M111 014613","DOI":"10.1074\/mcp.M111.014613","volume":"11","author":"JD Hoffert","year":"2012","unstructured":"Hoffert JD, Pisitkun T, Saeed F, Song JH, Chou CL, Knepper MA. Dynamics of the G protein-coupled vasopressin V2 receptor signaling network revealed by quantitative phosphoproteomics. Mol Cell Proteom. 2012;11:M111 014613.","journal-title":"Mol Cell Proteom"},{"key":"155_CR59","doi-asserted-by":"publisher","first-page":"15299","DOI":"10.1073\/pnas.1008461107","volume":"107","author":"K Xiao","year":"2010","unstructured":"Xiao K, Sun J, Kim J, Rajagopal S, Zhai B, Villen J, et al. Global phosphorylation analysis of beta-arrestin-mediated signaling downstream of a seven transmembrane receptor (7TMR). Proc Natl Acad Sci USA. 2010;107:15299\u2013304.","journal-title":"Proc Natl Acad Sci USA"},{"key":"155_CR60","doi-asserted-by":"publisher","unstructured":"Liu JJ, Sharma K, Zangrandi L, Chen C, Humphrey SJ, Chiu YT, et al. In vivo brain GPCR signaling elucidated by phosphoproteomics. Science. 2018;360. eaao4927 https:\/\/doi.org\/10.1126\/science.aao4927","DOI":"10.1126\/science.aao4927"},{"key":"155_CR61","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1111\/j.1369-1600.2010.00311.x","volume":"17","author":"J Bailey","year":"2012","unstructured":"Bailey J, Ma D, Szumlinski KK. Rapamycin attenuates the expression of cocaine-induced place preference and behavioral sensitization. Addict Biol. 2012;17:248\u201358.","journal-title":"Addict Biol"},{"key":"155_CR62","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1038\/mp.2015.211","volume":"21","author":"MM Harraz","year":"2016","unstructured":"Harraz MM, Tyagi R, Cortes P, Snyder SH. Antidepressant action of ketamine via mTOR is mediated by inhibition of nitrergic Rheb degradation. Mol Psychiatry. 2016;21:313\u20139.","journal-title":"Mol Psychiatry"},{"key":"155_CR63","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.cellsig.2017.01.016","volume":"32","author":"SS Schattauer","year":"2017","unstructured":"Schattauer SS, Kuhar JR, Song A, Chavkin C. Nalfurafine is a G-protein biased agonist having significantly greater bias at the human than rodent form of the kappa opioid receptor. Cell Signal. 2017;32:59\u201365.","journal-title":"Cell Signal"},{"key":"155_CR64","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1016\/j.neuropharm.2015.08.027","volume":"99","author":"J Morgenweck","year":"2015","unstructured":"Morgenweck J, Frankowski KJ, Prisinzano TE, Aube J, Bohn LM. Investigation of the role of betaarrestin2 in kappa opioid receptor modulation in a mouse model of pruritus. Neuropharmacology. 2015;99:600\u20139.","journal-title":"Neuropharmacology"},{"key":"155_CR65","doi-asserted-by":"publisher","first-page":"ra117","DOI":"10.1126\/scisignal.aai8441","volume":"9","author":"TF Brust","year":"2016","unstructured":"Brust TF, Morgenweck J, Kim SA, Rose JH, Locke JL, Schmid CL, et al. Biased agonists of the kappa opioid receptor suppress pain and itch without causing sedation or dysphoria. Sci Signal. 2016;9:ra117.","journal-title":"Sci Signal"}],"container-title":["Neuropsychopharmacology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/s41386-018-0155-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41386-018-0155-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41386-018-0155-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,5]],"date-time":"2025-07-05T22:40:26Z","timestamp":1751755226000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41386-018-0155-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7,20]]},"references-count":65,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2019,4]]}},"alternative-id":["155"],"URL":"https:\/\/doi.org\/10.1038\/s41386-018-0155-0","relation":{},"ISSN":["0893-133X","1740-634X"],"issn-type":[{"value":"0893-133X","type":"print"},{"value":"1740-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,7,20]]},"assertion":[{"value":"26 January 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 July 2018","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 July 2018","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 July 2018","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}