Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
Department of Neurobiology, Institute for Biological Research, University of Belgrade, 11000 Belgrade, Serbia.
Cells. 2024 Aug 26;13(17):1425. doi: 10.3390/cells13171425.
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.
精神分裂症（SCH）是一种需要长期抗精神病药物治疗的精神障碍。SCH 患者被认为对压力更敏感。SCH 中观察到的下丘脑-垂体-肾上腺（HPA）轴失调可能包括糖皮质激素、糖皮质激素受体（GR）和相关蛋白水平的改变。在啮齿动物中给予苯环己哌啶（PCP）是 SCH 的动物模型。本研究调查了围产期 PCP 暴露以及随后的氟哌啶醇/氯氮平治疗对 ELISA 测量的皮质酮水平和 Western blot 确定的 GR 相关蛋白（GR、pGR、HSP70、HSP90、FKBP51 和 11β-羟类固醇脱氢酶-11β-HSD）表达的影响成年大鼠的不同脑区。六组雄性大鼠在出生后第 2、6、9 和 12 天（PN）用 PCP 或生理盐水处理。随后，一组生理盐水和一组 PCP 组从 PN 第 35 天到 PN 第 100 天接受氟哌啶醇/氯氮平治疗。结果表明，PCP 暴露后大鼠大脑中的 GR 敏感性发生改变，氟哌啶醇/氯氮平治疗后降低。这些发现强调了 HPA 轴在 PCP 诱导的 SCH 模型中的紊乱和抗精神病药物的潜在保护作用。据我们所知，这是第一项研究抗精神病药物对 SCH 的 PCP 动物模型中 HPA 轴的影响的研究。
