3-(4-甲氧基苯基)selanyl)-2-苯基苯并呋喃(SeBZF3)对小鼠的类似焦虑作用:5-羟色胺能系统的可能贡献。

IF 3.3 3区 心理学 Q1 BEHAVIORAL SCIENCES
Larissa Sander Magalhães , Dianer Nornberg Strelow , Mariana Parron Paim , Taís da Silva Teixeira Rech , Letícia Devantier Krüger , Antonio Luiz Braga , José Sebastião Santos Neto , César Augusto Brüning , Cristiani Folharini Bortolatto
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引用次数: 0

摘要

以高患病率为特征的焦虑症会导致精神残疾,并与血清素能系统功能受损有关。频繁的焦虑复发、耐药性和药物不良反应促使人们寻找新的治疗方法。我们使用明暗试验(LDT)初步评估了3-烯基-苯并[b]呋喃化合物(SeBZF1-5)(50 mg/kg,i.g.)在雄性瑞士小鼠中的抗焦虑样活性。化合物3-((4-甲氧基苯基)selanyl)-2-苯基苯并呋喃(SeBZF3)具有抗焦虑活性。在新颖性抑制喂养试验(NSFT)(50 mg/kg)和升高加迷宫试验(EPMT)(25和50 mg/kg)中也观察到SeBZF3的抗焦虑样作用。在EPMT中,SeBZF3(50 mg/kg)的抗焦虑样作用通过用选择性色氨酸羟化酶抑制剂对氯苯基丙氨酸(100 mg/kg,腹腔注射4天)预处理而消除,这表明涉及5-羟色胺能机制。此外,我们进行了实验来研究SeBZF3亚有效剂量(5 mg/kg,i.g.)与氟西汀(一种选择性血清素再摄取抑制剂,5 mg/kg,腹膜内)或丁螺环酮(一种5-HT1A受体的部分激动剂,2 mg/kg,腹膜外)联合使用的协同作用。我们还研究了SeBZF3在14天内以1和5 mg/kg的剂量重复口服治疗的效果,这两种治疗都降低了焦虑信号。体外和离体研究结果表明,SeBZF3抑制脑MAO-A活性。这些发现共同暗示了SeBZF3在小鼠中的抗焦虑样活性可能涉及5-羟色胺能机制。这些数据为有机硒化合物和抗焦虑药的研究领域做出了贡献,鼓励扩大对新型有效药物的搜索,同时改善副作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Anxiolytic-like action of 3-((4-methoxyphenyl)selanyl)-2-phenylbenzofuran (SeBZF3) in mice: A possible contribution of the serotonergic system

Anxiolytic-like action of 3-((4-methoxyphenyl)selanyl)-2-phenylbenzofuran (SeBZF3) in mice: A possible contribution of the serotonergic system

Anxiety disorders, characterized by high prevalence rates, cause psychiatric disabilities and are related to impairments in serotoninergic system function. Frequent anxiety recurrence, resistance, and drug adverse effects have driven searches for new therapies. We initially evaluated the anxiolytic-like activity of 3-selanyl-benzo[b]furan compounds (SeBZF1–5) (50 mg/kg, i.g.) in male Swiss mice using the light-dark test (LDT). The compound 3-((4-methoxyphenyl)selanyl)-2-phenylbenzofuran (SeBZF3) exhibited anxiolytic-like activity. SeBZF3 anxiolytic-like effects were also observed in the novelty-suppressed feeding test (NSFT) (50 mg/kg) and elevated plus-maze test (EPMT) (25 and 50 mg/kg). In the EPMT, anxiolytic-like effects of SeBZF3 (50 mg/kg) were abolished by pretreatment with p-chlorophenylalanine, a selective tryptophan hydroxylase inhibitor (100 mg/kg, i.p. for 4 days), suggesting the involvement of serotonergic mechanisms. Furthermore, we conducted experiments to investigate the synergistic effects of SeBZF3 subeffective doses (5 mg/kg, i.g.) in combination with fluoxetine (a selective serotonin reuptake inhibitor, 5 mg/kg, i.p.) or buspirone (a partial agonist of the 5-HT1A receptor, 2 mg/kg, i.p.). This coadministration resulted in pronounced synergistic effects. We also examined the effects of repeated oral treatment with SeBZF3 at doses of 1 and 5 mg/kg over 14 days and both reduced anxiety signals. In vitro and ex vivo findings revealed that SeBZF3 inhibited cerebral MAO-A activity. These findings collectively imply the potential involvement of serotonergic mechanisms in the anxiolytic-like activity of SeBZF3 in mice. These data offer contributions to the research field of organoselenium compounds and anxiolytics, encouraging the broadening of the search for new effective drugs while offering improved side effect profiles.

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来源期刊
CiteScore
6.40
自引率
2.80%
发文量
122
审稿时长
38 days
期刊介绍: Pharmacology Biochemistry & Behavior publishes original reports in the areas of pharmacology and biochemistry in which the primary emphasis and theoretical context are behavioral. Contributions may involve clinical, preclinical, or basic research. Purely biochemical or toxicology studies will not be published. Papers describing the behavioral effects of novel drugs in models of psychiatric, neurological and cognitive disorders, and central pain must include a positive control unless the paper is on a disease where such a drug is not available yet. Papers focusing on physiological processes (e.g., peripheral pain mechanisms, body temperature regulation, seizure activity) are not accepted as we would like to retain the focus of Pharmacology Biochemistry & Behavior on behavior and its interaction with the biochemistry and neurochemistry of the central nervous system. Papers describing the effects of plant materials are generally not considered, unless the active ingredients are studied, the extraction method is well described, the doses tested are known, and clear and definite experimental evidence on the mechanism of action of the active ingredients is provided.
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