当前位置： SCI文献检索 > EUROPEAN JOURNAL OF PHARMACOLOGY期刊下所有文献 > Flesinoxan treatment reduces 5-HT1A receptor mRNA in the dentate gyrus independently of high plasma corticosterone levels.

Flesinoxan treatment reduces 5-HT1A receptor mRNA in the dentate gyrus independently of high plasma corticosterone levels.

Abstract：

:Flesinoxan acts as a full 5-HT1A receptor agonist and displays anxiolytic and anti-depressant properties. 5-HT1A receptor agonists, including flesinoxan, increase corticosterone (B) levels in the blood and reduces 5-HT1A receptor mRNA expression in the hippocampus. In this study, we examined whether the 5-HT1A receptor downregulation induced by flesinoxan involves corticosterone control of 5-HT1A receptor gene transcription. In experiment I, intact male Wistar rats (180-200 g) were treated with flesinoxan (1.0, 3.0 and 10 mg/kg bw, sc) or vehicle and decapitated 3 h later. Flesinoxan administration resulted in a significant, dose-dependent downregulation of 5-HT1A receptor mRNA in the dentate gyrus and dorsal raphe nucleus. In experiment II, rats were sham-operated and implanted with a cholesterol pellet (100 mg) or were adrenalectomized and implanted with a corticosterone pellet (20 mg corticosterone + 80 mg cholesterol). Flesinoxan injection also caused a dose-dependent decrease of 5-HT1A mRNA in the dentate gyrus of adrenalectomized animals with corticosterone replacement. There was no effect in the dorsal raphe nucleus. In experiment III, adrenalectomized and adrenalectomized + corticosterone rats were sc injected with flesinoxan (10 mg/kg bw) or vehicle, and flesinoxan appeared to downregulate 5-HT1A receptor expression in the dentate gyrus independently of corticosterone as well. No significant effects were observed in the dorsal raphe nucleus. It is concluded that flesinoxan reduces 5-HT1A receptor expression in the dentate gyrus both through homologous downregulation and a corticosterone-mediated effect on the serotonergic (5-HT) system.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Sibug RM,Compaan JC,Meijer OC,Van der Gugten J,Olivier B,De Kloet ER

doi

10.1016/s0014-2999(98)00417-8

subject

Has Abstract

pub_date

1998-07-24 00:00:00

pages

207-14

issue

2-3

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(98)00417-8

journal_volume

353

pub_type

杂志文章

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