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地塞米松急性给药致抑郁样行为和认知障碍:2-苯基-3-(苯硒基)苯并呋喃在雌性瑞士小鼠中的药理作用。

Depressive-like behavior and cognitive impairment induced by acute administration of dexamethasone: Pharmacological effects of 2-phenyl-3-(phenylselanyl)benzofuran in female Swiss mice.

机构信息

Programa de Pós-graduação em Bioquímica e Bioprospecção, Laboratório de Bioquímica e Neurofarmacologia Molecular (LABIONEM), Grupo de Pesquisa em Neurobiotecnologia (GPN), Centro de Ciências Químicas, Farmacêuticas e de Alimentos (CCQFA), Universidade Federal de Pelotas (UFPel), CEP 96010-900 Pelotas, RS, Brazil.

Instituto de Química - Universidade Federal de Goiás - UFG, CEP 74.690-900 Goiânia, Goiás, Brazil.

出版信息

Prog Neuropsychopharmacol Biol Psychiatry. 2023 Jul 13;125:110772. doi: 10.1016/j.pnpbp.2023.110772. Epub 2023 Apr 17.

DOI:10.1016/j.pnpbp.2023.110772
PMID:37075882
Abstract

Synthetic glucocorticoid administration has been reported to play a role in depression and cognitive decline. The present study investigated the 2-phenyl-3-(phenylselanyl)benzofuran (SeBZF1) effects against the depressive-like behavior, memory impairment, and neurochemical alterations caused by acute dexamethasone administration in female Swiss mice. A dexamethasone dose-response curve (0.07-0.5 mg/kg, subcutaneous route, s.c.) was initially performed to validate the depressive-like behavior induction, in which the 0.25 mg/kg dose was more effective. Two experimental sets were performed to test the SeBZF1 (5 and 50 mg/kg, intragastric route, i.g.) pharmacological effect in this animal model. The 1st set revealed that the SeBZF1 reverses the dexamethasone-induced depressive-like behavior in the tail suspension test and in the splash test. In the 2nd experimental set, the compound effects of reversing the depressive-like behavior in the forced swimming test and the memory deficit in the Y-maze test induced by acute treatment with dexamethasone were demonstrated. Furthermore, SeBZF1 reversed the increase in the monoamine oxidase (MAO) activity in the prefrontal cortex (isoforms A and B) and in the hypothalamus (isoform A) caused by dexamethasone. However, no changes were observed in hippocampal MAO activity. Furthermore, animals treated with dexamethasone and SeBZF1 demonstrated a partially lower acetylcholinesterase activity in the prefrontal cortex compared with the induced group. In summary, the present study demonstrated that SeBZF1 reverses depressive-like behavior and memory deficits caused by acute dexamethasone treatment in female Swiss mice. Possibly the compound exerts its antidepressant-like action by increasing the availability of monoamines, while its effects on memory are still partially understood.

摘要

合成糖皮质激素的应用已被报道在抑郁症和认知能力下降中发挥作用。本研究旨在探讨 2-苯基-3-(苯硒基)苯并呋喃(SeBZF1)对急性地塞米松给药引起的雌性瑞士小鼠抑郁样行为、记忆障碍和神经化学改变的作用。首先进行了地塞米松剂量反应曲线(0.07-0.5mg/kg,皮下给药,sc),以验证抑郁样行为诱导,其中 0.25mg/kg 剂量更有效。进行了两项实验来测试 SeBZF1(5 和 50mg/kg,灌胃给药,ig)在该动物模型中的药理学作用。第一组实验表明,SeBZF1 逆转了地塞米松诱导的悬尾试验和溅水试验中的抑郁样行为。在第二组实验中,证明了 SeBZF1 逆转了急性地塞米松处理引起的强迫游泳试验中的抑郁样行为和 Y 迷宫试验中的记忆缺陷。此外,SeBZF1 逆转了地塞米松引起的前额叶皮层(A 和 B 同工型)和下丘脑(同工型 A)中单胺氧化酶(MAO)活性的增加。然而,海马 MAO 活性没有变化。此外,与诱导组相比,用地塞米松和 SeBZF1 处理的动物在前额叶皮层中的乙酰胆碱酯酶活性部分降低。总之,本研究表明,SeBZF1 逆转了急性地塞米松处理引起的雌性瑞士小鼠的抑郁样行为和记忆缺陷。该化合物可能通过增加单胺类物质的可利用性发挥其抗抑郁作用,而其对记忆的影响仍部分未知。

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