{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T07:27:53Z","timestamp":1790148473024,"version":"4.0.1"},"reference-count":177,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2017,1,12]],"date-time":"2017-01-12T00:00:00Z","timestamp":1484179200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Dopamine-glutamate interplay dysfunctions have been suggested as pathophysiological key determinants of major psychotic disorders, above all schizophrenia and mood disorders. For the most part, synaptic interactions between dopamine and glutamate signaling pathways take part in the postsynaptic density, a specialized ultrastructure localized under the membrane of glutamatergic excitatory synapses. Multiple proteins, with the role of adaptors, regulators, effectors, and scaffolds compose the postsynaptic density network. They form structural and functional crossroads where multiple signals, starting at membrane receptors, are received, elaborated, integrated, and routed to appropriate nuclear targets. Moreover, transductional pathways belonging to different receptors may be functionally interconnected through postsynaptic density molecules. Several studies have demonstrated that psychopharmacologic drugs may differentially affect the expression and function of postsynaptic genes and proteins, depending upon the peculiar receptor profile of each compound. Thus, through postsynaptic network modulation, these drugs may induce dopamine-glutamate synaptic remodeling, which is at the basis of their long-term physiologic effects. In this review, we will discuss the role of postsynaptic proteins in dopamine-glutamate signals integration, as well as the peculiar impact of different psychotropic drugs used in clinical practice on postsynaptic remodeling, thereby trying to point out the possible future molecular targets of \u201csynapse-based\u201d psychiatric therapeutic strategies.<\/jats:p>","DOI":"10.3390\/ijms18010135","type":"journal-article","created":{"date-parts":[[2017,1,12]],"date-time":"2017-01-12T10:02:08Z","timestamp":1484215328000},"page":"135","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["Treating the Synapse in Major Psychiatric Disorders: The Role of Postsynaptic Density Network in Dopamine-Glutamate Interplay and Psychopharmacologic Drugs Molecular Actions"],"prefix":"10.3390","volume":"18","author":[{"given":"Carmine","family":"Tomasetti","sequence":"first","affiliation":[{"name":"NHS, Department of Mental Health ASL Teramo, Psychiatric Service of Diagnosis and Treatment, Hospital \u201cMaria SS dello Splendore\u201d, 641021 Giulianova, Italy"},{"name":"Laboratory of Molecular and Translational Psychiatry, Department of Neuroscience, Reproductive and Odontostomatogical Sciences, University of Naples \u201cFederico II\u201d, 80131 Napoli, Italy"},{"name":"Polyedra Research Group, 64100 Teramo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felice","family":"Iasevoli","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Translational Psychiatry, Department of Neuroscience, Reproductive and Odontostomatogical Sciences, University of Naples \u201cFederico II\u201d, 80131 Napoli, Italy"},{"name":"Polyedra Research Group, 64100 Teramo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Buonaguro","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Translational Psychiatry, Department of Neuroscience, Reproductive and Odontostomatogical Sciences, University of Naples \u201cFederico II\u201d, 80131 Napoli, Italy"},{"name":"Polyedra Research Group, 64100 Teramo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4415-5058","authenticated-orcid":false,"given":"Domenico","family":"De Berardis","sequence":"additional","affiliation":[{"name":"Polyedra Research Group, 64100 Teramo, Italy"},{"name":"NHS, Department of Mental Health ASL Teramo, Psychiatric Service of Diagnosis and Treatment, Hospital \u201cG. Mazzini\u201d, 64100 Teramo, Italy"},{"name":"Department of Neuroscience and Imaging, University \u201cG. d\u2019Annunzio\u201d, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Fornaro","sequence":"additional","affiliation":[{"name":"Polyedra Research Group, 64100 Teramo, Italy"},{"name":"New York State Psychiatric Institute, Columbia University, New York, NY 10027, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annastasia","family":"Fiengo","sequence":"additional","affiliation":[{"name":"Polyedra Research Group, 64100 Teramo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Martinotti","sequence":"additional","affiliation":[{"name":"Polyedra Research Group, 64100 Teramo, Italy"},{"name":"Department of Neuroscience and Imaging, University \u201cG. d\u2019Annunzio\u201d, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6882-3770","authenticated-orcid":false,"given":"Laura","family":"Orsolini","sequence":"additional","affiliation":[{"name":"Polyedra Research Group, 64100 Teramo, Italy"},{"name":"Casa di Cura Villa San Giuseppe, 63100 Ascoli Piceno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Valchera","sequence":"additional","affiliation":[{"name":"Polyedra Research Group, 64100 Teramo, Italy"},{"name":"Casa di Cura Villa San Giuseppe, 63100 Ascoli Piceno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Di Giannantonio","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Imaging, University \u201cG. d\u2019Annunzio\u201d, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"De Bartolomeis","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Translational Psychiatry, Department of Neuroscience, Reproductive and Odontostomatogical Sciences, University of Naples \u201cFederico II\u201d, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,1,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1146\/annurev.biochem.76.060805.160029","article-title":"The postsynaptic architecture of excitatory synapses: A more quantitative view","volume":"76","author":"Sheng","year":"2007","journal-title":"Annu. 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