Effects of Antipsychotics on the Hypothalamus-Pituitary-Adrenal Axis in a Phencyclidine Animal Model of Schizophrenia.

Autor: Nikolić T; Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia., Bogosavljević MV; Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia., Stojković T; Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia., Kanazir S; Department of Neurobiology, Institute for Biological Research, University of Belgrade, 11000 Belgrade, Serbia., Lončarević-Vasiljković N; iNOVA4Health, NOVA Medical School|Faculdade Ciências Médicas, NMS|FCM, Universidade Nova de Lisboa, Campo dos Mártires da Pátria, 1169-056 Lisbon, Portugal., Radonjić NV; Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, NY 13210, USA., Popić J; Department of Neurology and Neurosurgery, McGill University, Montreal, QC H3A 0G4, Canada., Petronijević N; Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
Jazyk: angličtina
Zdroj: Cells [Cells] 2024 Aug 26; Vol. 13 (17). Date of Electronic Publication: 2024 Aug 26.
DOI: 10.3390/cells13171425
Abstrakt: Schizophrenia (SCH) is a mental disorder that requires long-term antipsychotic treatment. SCH patients are thought to have an increased sensitivity to stress. The dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, observed in SCH, could include altered levels of glucocorticoids, glucocorticoid receptors (GRs), and associated proteins. The perinatal administration of phencyclidine (PCP) to rodents represents an animal model of SCH. This study investigated the effects of perinatal PCP exposure and subsequent haloperidol/clozapine treatment on corticosterone levels measured by ELISA and the expression of GR-related proteins (GR, pGR, HSP70, HSP90, FKBP51, and 11β-Hydroxysteroid dehydrogenase-11β-HSD) determined by Western blot, in different brain regions of adult rats. Six groups of male rats were treated on the 2nd, 6th, 9th, and 12th postnatal days (PN), with either PCP or saline. Subsequently, one saline and one PCP group received haloperidol/clozapine from PN day 35 to PN day 100. The results showed altered GR sensitivity in the rat brain after PCP exposure, which decreased after haloperidol/clozapine treatment. These findings highlight disturbances in the HPA axis in a PCP-induced model of SCH and the potential protective effects of antipsychotics. To the best of our knowledge, this is the first study to investigate the effects of antipsychotic drugs on the HPA axis in a PCP animal model of SCH.
Databáze: MEDLINE