Effects of Antipsychotics on the Hypothalamus-Pituitary-Adrenal Axis in a Phencyclidine Animal Model of Schizophrenia.
Tatjana Nikolić, Milica Velimirović Bogosavljević, Tihomir Stojković, Selma Kanazir, Nataša Lončarević-vasiljković, Nevena V Radonjić, Jelena Popić, Nataša Petronijević
Cells August 26, 2024 Peer reviewed DOI: 10.3390/cells13171425 via PubMed
Summary
Perinatal exposure to phencyclidine (PCP) in rats, an animal model of schizophrenia, resulted in altered glucocorticoid receptor sensitivity in the brain. Treatment with antipsychotics haloperidol and clozapine later decreased this altered sensitivity. These findings suggest that PCP exposure disrupts the hypothalamic-pituitary-adrenal (HPA) axis, but antipsychotic treatment may offer protective effects against these disturbances.
Study at a glance
| Design | experimental study |
|---|---|
| Population | male rats |
| Key finding | Altered glucocorticoid receptor sensitivity in the rat brain after PCP exposure decreased following haloperidol/clozapine treatment. |
Abstract
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.