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 DOI: 10.3390/cells13171425 via PubMed
Summary
AI-generated from the abstractIn a rat model of schizophrenia created by perinatal phencyclidine (PCP) exposure, antipsychotic treatment with haloperidol or clozapine reduced altered glucocorticoid receptor (GR) sensitivity in the brain. The study measured corticosterone levels and GR-related proteins (GR, pGR, HSP70, HSP90, FKBP51, and 11β-HSD) in different brain regions of adult male rats. Six groups were treated with PCP or saline on postnatal days 2, 6, 9, and 12; some groups then received haloperidol or clozapine from day 35 to 100. The findings indicate disturbances in the HPA axis in this schizophrenia model and suggest antipsychotics may have protective effects against such dysregulation.
Study at a glance
| Characteristics | Controlled experiment Peer reviewed |
|---|---|
| Sample size | 6 |
| Population | Male rats |
| Interventions | PCP haloperidol clozapine |
| Duration | From postnatal day 35 to postnatal day 100 |
| Keywords | Hpa axis Animal model Antipsychotic Clozapine Corticosterone |
| Citations | 6 |
| Key finding | Perinatal PCP exposure altered GR sensitivity in the rat brain, which decreased after haloperidol or 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.