{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T15:09:53Z","timestamp":1789052993038,"version":"build-2803163510"},"reference-count":108,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2019,3,21]],"date-time":"2019-03-21T00:00:00Z","timestamp":1553126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Polish National Centre for Research and Development","award":["POIG.01.04.00-04-219\/12"],"award-info":[{"award-number":["POIG.01.04.00-04-219\/12"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Schizophrenia is a chronic mental disease, affecting around 1% of the general population. Schizophrenia is characterized by productive, negative, affective, and disorganization symptoms, and cognitive deficits. Cognitive deficits prevail in most of the schizophrenia patients and are one of the most disabling symptoms. They usually occur before the acute episode of the disease and tend to become chronic with no satisfactory treatment from antipsychotic drugs. Because of their early manifestation in patients\u2019 lives, cognitive deficits are suggested to be the primary symptom of schizophrenia. The pathogenesis of cognitive deficits in schizophrenia is not fully understood. They are linked with hypofrontality, which is a decrease in blood flow and glucose metabolism in the prefrontal lobe of schizophrenia-suffering patients. Hypofrontality is linked with disturbances of the corticolimbothalamic circuit, important for cognition and memory in humans. The circuit consists of a group of neuroanatomic structures and hypothetically any disturbance in them may result in cognitive deficits. We present a translational preclinical model of understanding how antipsychotic medication may decrease the N-methyl-D-aspartic acid (NMDA) receptors\u2019 activity and produce dysfunctions in the corticolimbothalamic circuit and hypofrontality. From several pharmacological experiments on rats, including mainly our own recent findings, we collected data that suggest that antipsychotic medication may maintain and escalate hypofrontality in schizophrenia, decreasing NMDA receptor activity in the corticolimbothalamic circuit in the human brain. We discuss our findings within the literature of the subject.<\/jats:p>","DOI":"10.3390\/ijms20061442","type":"journal-article","created":{"date-parts":[[2019,3,21]],"date-time":"2019-03-21T12:28:01Z","timestamp":1553171281000},"page":"1442","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["NMDA Receptor Model of Antipsychotic Drug-Induced Hypofrontality"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1665-7344","authenticated-orcid":false,"given":"Marek","family":"Krzystanek","sequence":"first","affiliation":[{"name":"Department and Clinic of Psychiatric Rehabilitation, Department of Psychiatry and Psychotherapy, School of Medicine in Katowice, Zio\u0142owa 45\/47, 40-635 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artur","family":"Pa\u0142asz","sequence":"additional","affiliation":[{"name":"Department of Histology, School of Medicine in Katowice, Medyk\u00f3w 18, 40-752 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,3,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1001\/archpsyc.64.1.19","article-title":"Lifetime Prevalence of Psychotic and Bipolar I Disorders in a General Population","volume":"64","author":"Suvisaari","year":"2007","journal-title":"Arch. 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