Hyperactivity of the hypothalamus–pituitary–adrenal axis in lipopolysaccharide-induced neurodevelopmental model of schizophrenia in rats: Effects of antipsychotic drugs

详细信息    查看全文

• 作者：Agnieszka Basta-Kaim ; Bogusł ; awa Budziszewska ; Monika Leś ; kiewicz ; Katarzyna Fijał ; Magdalena Regulska ; Marta Kubera ; Krzysztof Wę ; dzony ; Wł ; adysł ; aw Lasoń
• 关键词：Neurodevelopmental model of schizophrenia ; HPA axis activity ; Glucocorticoid receptor ; FKBP51 ; Sensorimotor gating ; Locomotor activity
• 刊名：European Journal of Pharmacology
• 出版年：2011
• 出版时间：15 January 2011
• 年：2011
• 卷：650
• 期：2-3
• 页码：586-595
• 全文大小：1267 K

文摘

Recent data indicate that a significant number of schizophrenic patients are hypercortisolemic and that glucocorticoids are involved in the pathogenesis of schizophrenia. The aim of the present study was to evaluate whether behavioural schizophrenia-like changes in the lipopolysaccharide (LPS)-induced neurodevelopmental model of this brain disorder are associated with alterations in the level of plasma corticosterone, the concentration of glucocorticoid receptors and the amount of the immunophilin FKBP51, the glucocorticoid receptor co-chaperone, in the hippocampus and frontal cortex. We found that the adult offspring of prenatally LPS-treated rats showed a deficit in prepulse inhibition (PPI), an enhancement of amphetamine-induced locomotor activity, an elevated plasma level of corticosterone and a decrease in both the glucocorticoid receptor level in the hippocampus and the FKBP51 concentration in the frontal cortex. Most of these changes were reversed by the atypical antipsychotic drug clozapine, whereas chlorpromazine had no effect on PPI but attenuated the amphetamine-induced hyperactivity and normalised the hippocampal level of glucocorticoid receptors. The changes in the level of plasma corticosterone and cortical FKBP51 were attenuated by chlorpromazine in female offspring only. This study supports the hypothesis of hypothalamic–pituitary–adrenal (HPA) axis hyperactivity in schizophrenia and suggests that this hyperactivity results from a decrease in the hippocampal glucocorticoid receptor level and a decrease in FKBP51 in the frontal cortex.