{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:15:57Z","timestamp":1791198957903,"version":"4.1.0"},"reference-count":21,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5649","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2003,11,21]]},"abstract":"<jats:p>Three distinct classes of drugs: dopaminergic agonists (such as D-amphetamine), serotonergic agonists (such as LSD), and glutamatergic antagonists (such as PCP) all induce psychotomimetic states in experimental animals that closely resemble schizophrenia symptoms in humans. Here we implicate a common signaling pathway in mediating these effects. In this pathway, dopamine- and an adenosine 3\u2032,5\u2032-monophosphate (cAMP)\u2013regulated phospho-protein of 32 kilodaltons (DARPP-32) is phosphorylated or dephosphorylated at three sites, in a pattern predicted to cause a synergistic inhibition of protein phosphatase\u20131 and concomitant regulation of its downstream effector proteins glycogen synthesis kinase\u20133 (GSK-3), cAMP response element\u2013binding protein (CREB), and c-Fos. In mice with a genetic deletion of DARPP-32 or with point mutations in phosphorylation sites of DARPP-32, the effects of D-amphetamine, LSD, and PCP on two behavioral parameters\u2014sensorimotor gating and repetitive movements\u2014were strongly attenuated.<\/jats:p>","DOI":"10.1126\/science.1089681","type":"journal-article","created":{"date-parts":[[2003,11,21]],"date-time":"2003-11-21T05:14:12Z","timestamp":1069391652000},"page":"1412-1415","source":"Crossref","is-referenced-by-count":273,"title":["Diverse Psychotomimetics Act Through a Common Signaling Pathway"],"prefix":"10.1126","volume":"302","author":[{"given":"Per","family":"Svenningsson","sequence":"first","affiliation":[{"name":"Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10021, USA."},{"name":"Eli Lilly and Company, Lilly Corporate Center, Neuroscience Discovery Research, Indianapolis, IN 46285\u20130510, USA."},{"name":"Lexicon Genetics Inc., The Woodlands, TX 77381\u20131160, USA."},{"name":"Intra-Cellular Therapies Inc., Audubon Biomedical Science and Technology Park, New York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni T.","family":"Tzavara","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10021, USA."},{"name":"Eli Lilly and Company, Lilly Corporate Center, Neuroscience Discovery Research, Indianapolis, IN 46285\u20130510, USA."},{"name":"Lexicon Genetics Inc., The Woodlands, TX 77381\u20131160, USA."},{"name":"Intra-Cellular Therapies Inc., Audubon Biomedical Science and Technology Park, New York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Carruthers","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10021, USA."},{"name":"Eli Lilly and Company, Lilly Corporate Center, Neuroscience Discovery Research, Indianapolis, IN 46285\u20130510, USA."},{"name":"Lexicon Genetics Inc., The Woodlands, TX 77381\u20131160, USA."},{"name":"Intra-Cellular Therapies Inc., Audubon Biomedical Science and Technology Park, New York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilan","family":"Rachleff","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10021, USA."},{"name":"Eli Lilly and Company, Lilly Corporate Center, Neuroscience Discovery Research, Indianapolis, IN 46285\u20130510, USA."},{"name":"Lexicon Genetics Inc., The Woodlands, TX 77381\u20131160, USA."},{"name":"Intra-Cellular Therapies Inc., Audubon Biomedical Science and Technology Park, New York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigrid","family":"Wattler","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10021, USA."},{"name":"Eli Lilly and Company, Lilly Corporate Center, Neuroscience Discovery Research, Indianapolis, IN 46285\u20130510, USA."},{"name":"Lexicon Genetics Inc., The Woodlands, TX 77381\u20131160, USA."},{"name":"Intra-Cellular Therapies Inc., Audubon Biomedical Science and Technology Park, New York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Nehls","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10021, USA."},{"name":"Eli Lilly and Company, Lilly Corporate Center, Neuroscience Discovery Research, Indianapolis, IN 46285\u20130510, USA."},{"name":"Lexicon Genetics Inc., The Woodlands, TX 77381\u20131160, USA."},{"name":"Intra-Cellular Therapies Inc., Audubon Biomedical Science and Technology Park, New York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L.","family":"McKinzie","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10021, USA."},{"name":"Eli Lilly and Company, Lilly Corporate Center, Neuroscience Discovery Research, Indianapolis, IN 46285\u20130510, USA."},{"name":"Lexicon Genetics Inc., The Woodlands, TX 77381\u20131160, USA."},{"name":"Intra-Cellular Therapies Inc., Audubon Biomedical Science and Technology Park, New York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen A.","family":"Fienberg","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10021, USA."},{"name":"Eli Lilly and Company, Lilly Corporate Center, Neuroscience Discovery Research, Indianapolis, IN 46285\u20130510, USA."},{"name":"Lexicon Genetics Inc., The Woodlands, TX 77381\u20131160, USA."},{"name":"Intra-Cellular Therapies Inc., Audubon Biomedical Science and Technology Park, New York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George G.","family":"Nomikos","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10021, USA."},{"name":"Eli Lilly and Company, Lilly Corporate Center, Neuroscience Discovery Research, Indianapolis, IN 46285\u20130510, USA."},{"name":"Lexicon Genetics Inc., The Woodlands, TX 77381\u20131160, USA."},{"name":"Intra-Cellular Therapies Inc., Audubon Biomedical Science and Technology Park, New York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Greengard","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10021, USA."},{"name":"Eli Lilly and Company, Lilly Corporate Center, Neuroscience Discovery Research, Indianapolis, IN 46285\u20130510, USA."},{"name":"Lexicon Genetics Inc., The Woodlands, TX 77381\u20131160, USA."},{"name":"Intra-Cellular Therapies Inc., Audubon Biomedical Science and Technology Park, New York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1070532"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.41.1.237"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-979353"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1988.01800310020002"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/378176a0"},{"key":"e_1_3_1_7_2","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1176\/ajp.155.6.761","volume":"155","year":"1998","unstructured":"A. Abi-Darghamet al., Am. J. Psychiatry155, 761 (1998).","journal-title":"Am. J. Psychiatry"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.124.3212.121"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneurpsyc.1959.02340150095011"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.130.1.61"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.294.5544.1024"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002130100811"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0301-0082(94)90039-6"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/npp.1994.22"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/310503a0"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(20)88248-9"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.7.2682"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/45251"},{"key":"e_1_3_1_19_2","unstructured":"P. Svenningsson R. Carruthers I. Rachleff P. Greengard unpublished observations."},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4001017"},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80245-7"},{"key":"e_1_3_1_22_2","unstructured":"Supported by the Stern Foundation and by NIH grants MH40899 and DA10044 (P.G.). P.S. is supported by a postdoctoral fellowship from Stiftelsen f\u00f6r Internationalisering av h\u00f6gre utbildning och forskning. We thank P. Ingrassia for help with animal breeding; G. L. Snyder J. A. Bibb A. C. Nairn and H. C. Hemmings Jr. for phospho-Thr 34 \u2013DARPP-32 phospho-Thr 75 DARPP-32 phospho-Ser 130 DARPP-32 and DARPP-32 antibodies; and K. Knitkowski and J. Camara for technical assistance."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1089681","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,14]],"date-time":"2024-12-14T12:36:29Z","timestamp":1734179789000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1089681"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,11,21]]},"references-count":21,"journal-issue":{"issue":"5649","published-print":{"date-parts":[[2003,11,21]]}},"alternative-id":["10.1126\/science.1089681"],"URL":"https:\/\/doi.org\/10.1126\/science.1089681","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,11,21]]}}}