{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T04:11:35Z","timestamp":1790395895651,"version":"4.1.0"},"reference-count":81,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,8,15]],"date-time":"2016-08-15T00:00:00Z","timestamp":1471219200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009412","name":"School of Pharmacy, University of Southern California","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009412","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Purinergic P2X4 receptors (P2X4Rs) belong to the P2X superfamily of ion channels regulated by<jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>. We recently demonstrated that P2X4R knockout (<jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content>) mice exhibited deficits in sensorimotor gating, social interaction, and ethanol drinking behavior. Dopamine (<jats:styled-content style=\"fixed-case\">DA<\/jats:styled-content>) dysfunction may underlie these behavioral changes, but there is no direct evidence for P2X4Rs\u2019 role in<jats:styled-content style=\"fixed-case\">DA<\/jats:styled-content>neurotransmission. To test this hypothesis, we measured markers of<jats:styled-content style=\"fixed-case\">DA<\/jats:styled-content>function and dependent behaviors in P2X4R<jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content>mice. P2X4R<jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content>mice exhibited altered density of pre\u2010synaptic markers including tyrosine hydroxylase, dopamine transporter; post\u2010synaptic markers including dopamine receptors and phosphorylation of downstream targets including dopamine and cyclic\u2010<jats:styled-content style=\"fixed-case\">AMP<\/jats:styled-content>regulated phosphoprotein of 32\u00a0kDa and cyclic\u2010<jats:styled-content style=\"fixed-case\">AMP<\/jats:styled-content>\u2010response element binding protein in different parts of the striatum. Ivermectin, an allosteric modulator of P2X4Rs, significantly affected dopamine and cyclic AMP regulated phosphoprotein of 32\u00a0kDa and extracellular regulated kinase1\/2 phosphorylation in the striatum. Sensorimotor gating deficits in P2X4R<jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content>mice were rescued by<jats:styled-content style=\"fixed-case\">DA<\/jats:styled-content>antagonists. Using the 6\u2010hydroxydopamine model of<jats:styled-content style=\"fixed-case\">DA<\/jats:styled-content>depletion, P2X4R<jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content>mice exhibited an attenuated levodopa (L\u2010<jats:styled-content style=\"fixed-case\">DOPA<\/jats:styled-content>)\u2010induced motor behavior, whereas ivermectin enhanced this behavior. Collectively, these findings identified an important role for P2X4Rs in maintaining<jats:styled-content style=\"fixed-case\">DA<\/jats:styled-content>homeostasis and illustrate how this association is important for<jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>functions including motor control and sensorimotor gating.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p><jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13734-fig-0007-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>We propose that P2X4 receptors (P2X4Rs) regulate dopamine (DA) homeostasis and associated behaviors. Pre\u2010synaptic and post\u2010synaptic DA markers were significantly altered in the dorsal and ventral striatum of P2X4R KO mice, implicating altered DA neurotransmission. Sensorimotor gating deficits in P2X4R KO mice were rescued by DA antagonists. Ivermectin (IVM), a positive modulator of P2X4Rs, enhanced levodopa (L\u2010DOPA)\u2010induced motor behavior. These studies highlight potential interactions between P2X4Rs and DA system.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13734","type":"journal-article","created":{"date-parts":[[2016,7,12]],"date-time":"2016-07-12T07:40:12Z","timestamp":1468309212000},"page":"134-148","source":"Crossref","is-referenced-by-count":44,"title":["Role of purinergic P2X4 receptors in regulating striatal dopamine homeostasis and dependent behaviors"],"prefix":"10.1111","volume":"139","author":[{"given":"Sheraz","family":"Khoja","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Pharmaceutical Sciences School of Pharmacy University of Southern California Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivek","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Neurology Keck School of Medicine University of Southern California Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damaris","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Neurology Keck School of Medicine University of Southern California Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liana","family":"Asatryan","sequence":"additional","affiliation":[{"name":"Titus Family Department of Clinical Pharmacy School of Pharmacy University of Southern California Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.","family":"Jakowec","sequence":"additional","affiliation":[{"name":"Department of Neurology Keck School of Medicine University of Southern California Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daryl L.","family":"Davies","sequence":"additional","affiliation":[{"name":"Titus Family Department of Clinical Pharmacy School of Pharmacy University of Southern California Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,8,15]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/026988119801200302"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11302-007-9069-8"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2006.08.018"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.110.167908"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1159\/000026690"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2011.07763.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1039-08.2008"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.103.049478"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145712000909"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/19.2.233"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.160.10.1836"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms150813344"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2005.03.032"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320600203"},{"key":"e_1_2_7_16_1","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1016\/S0022-3565(24)39005-6","article-title":"Anticonvulsant and adverse effects of avermectin analogs in mice are mediated through the gamma\u2010aminobutyric acid A receptor","volume":"295","author":"Dawson G. R.","year":"2000","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.2002.7891"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1301657"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ntt.2011.09.001"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2004.01.008"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867033457700"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2000.00876.x"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2008.06.004"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(00)00238-7"},{"key":"e_1_2_7_25_1","volume-title":"The Mouse Brain in Stereotaxic Coordinates","author":"Franklin B. J.","year":"2007"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-4328(00)00193-5"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2008.09.011"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-7091-0932-8_18"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/39639"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-009-9924-5"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11010"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2007.07.015"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(95)91801-9"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-9964(98)00113-3"},{"key":"e_1_2_7_35_1","doi-asserted-by":"crossref","first-page":"2121","DOI":"10.1523\/JNEUROSCI.20-06-02121.2000","article-title":"Presynaptic P2X receptors facilitate inhibitory GABAergic transmission between cultured rat spinal cord dorsal horn neurons","volume":"20","author":"Hugel S.","year":"2002","journal-title":"J. Neurosci."},{"key":"e_1_2_7_36_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1037\/0033-2909.94.1.3","article-title":"Reflex modification in the domain of startle: II. The anomalous history of a robust and ubiquitous phenomenon","volume":"94","author":"Ison J. R.","year":"1983","journal-title":"Psychol. Bull."},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.08.084"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-008-0450-4"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.231324"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4000989"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.09.024"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-17-07289.1999"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.105.087437"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.53.2.283"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(00)01040-5"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(01)00033-8"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/syn.10162"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1097\/00008877-199811000-00012"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(97)00365-5"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-183X.2010.00615.x"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00015.2002"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2014.10.016"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1995.03950180057008"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0278-5846(03)00106-4"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3223(01)01184-2"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11302-013-9373-4"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.200308986"},{"key":"e_1_2_7_58_1","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1523\/JNEUROSCI.21-01-00305.2001","article-title":"Prepulse inhibition deficits and perseverative motor patterns in dopamine transporter knock\u2010out mice: differential effects of D1 and D2 receptor antagonists","volume":"21","author":"Ralph R. J.","year":"2001","journal-title":"J. Neurosci."},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-21-09604.2002"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1300017"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-4328(03)00187-6"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(96)00040-8"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2013.07.006"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2013.06.005"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/syn.20303"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M011264200"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2370-06.2006"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.44.101802.121415"},{"key":"e_1_2_7_69_1","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/S0022-3565(25)23018-X","article-title":"Effects of spiperone, raclopride, SCH 23390 and clozapine on apomorphine inhibition of sensorimotor gating of the startle response in the rat","volume":"256","author":"Swerdlow N. R.","year":"1991","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_7_70_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-008-1072-4"},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2308-08.2008"},{"key":"e_1_2_7_72_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-201X.1971.tb11000.x"},{"key":"e_1_2_7_73_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145711001787"},{"key":"e_1_2_7_74_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-183X.2006.00292.x"},{"key":"e_1_2_7_75_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2013.98"},{"key":"e_1_2_7_76_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-014-1271-9"},{"key":"e_1_2_7_77_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.108.139766"},{"key":"e_1_2_7_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2010.08.099"},{"key":"e_1_2_7_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2012.03.014"},{"key":"e_1_2_7_80_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00558.2009"},{"key":"e_1_2_7_81_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.2010.01128.x"},{"key":"e_1_2_7_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/0741-8329(95)00010-O"}],"container-title":["Journal of Neurochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjnc.13734","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjnc.13734","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jnc.13734","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T00:40:03Z","timestamp":1748997603000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jnc.13734"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,8,15]]},"references-count":81,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2016,10]]}},"alternative-id":["10.1111\/jnc.13734"],"URL":"https:\/\/doi.org\/10.1111\/jnc.13734","archive":["Portico"],"relation":{},"ISSN":["0022-3042","1471-4159"],"issn-type":[{"value":"0022-3042","type":"print"},{"value":"1471-4159","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,8,15]]}}}