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普萘洛尔和纳多洛尔对社交挫败诱导的大鼠行为损伤的保护作用。

Protective effect of propranolol and nadolol on social defeat-induced behavioral impairments in rats.

机构信息

Department of Pharmacological and Pharmaceutical Sciences, University of Houston, Houston, Texas, USA.

Department of Pharmacological and Pharmaceutical Sciences, University of Houston, Houston, Texas, USA.

出版信息

Neurosci Lett. 2020 Apr 23;725:134892. doi: 10.1016/j.neulet.2020.134892. Epub 2020 Mar 9.

Abstract

Benzodiazepines and SSRIs are considered as standard treatment options for anxiety and depression, hallmarks of Post-Traumatic Stress Disorder (PTSD), although their use is often limited by adverse effects. While promising evidence emerged with β-adrenergic receptor (β-AR) antagonists (or 'β-blockers') and PTSD relief, efficacy issues dampened the excitement. However, we believe it is premature to completely eliminate a beneficial role of β-blockers. Our previous work has suggested that social defeat (SD) results in anxiety-like and depression-like behaviors in rats. Here, using the SD paradigm, we examined the effect of several β-adrenergic receptor antagonists (propranolol, nadolol, bisoprolol) on these behaviors in rats. Following acclimatization, Sprague-Dawley rats received no treatment (for control groups) or treated with ; propranolol (50 mg/kg/day in water), or nadolol (18 mg/kg/day in rats' chow), or bisoprolol (15 mg/kg/day in water). The treatment lasted for 36 days, following which rats were subjected to SD/control exposures (1 week). Later, anxiety-like and depression-like behaviors, social interaction and learning-memory function tests were conducted. SD rats exhibited anxiety- and depression-like behavior as well as learning-memory impairment. Propranolol and nadolol protected SD rats from exhibiting anxiety-or depression-like behaviors. Bisoprolol treatment did not mitigate SD-induced behavioral impairments in rats. Nadolol, propranolol or bisoprolol have no effect in attenuating SD-induced memory function tests. These results suggest that certain 'β-blockers' have the potential to mitigate the negative psychological effects of traumatic events.

摘要

苯二氮䓬类药物和 SSRI 被认为是焦虑和抑郁的标准治疗选择,也是创伤后应激障碍 (PTSD) 的特征,但由于不良反应,其使用往往受到限制。虽然β-肾上腺素能受体 (β-AR) 拮抗剂(或“β-阻滞剂”)和 PTSD 缓解的有希望的证据出现了,但疗效问题降低了兴奋度。然而,我们认为完全消除β-阻滞剂的有益作用还为时过早。我们之前的工作表明,社会挫败(SD)会导致大鼠出现类似焦虑和抑郁的行为。在这里,我们使用 SD 范式,研究了几种β-肾上腺素能受体拮抗剂(普萘洛尔、纳多洛尔、比索洛尔)对大鼠这些行为的影响。在适应环境后,Sprague-Dawley 大鼠接受无治疗(对照组)或以下治疗:普萘洛尔(50mg/kg/天,溶于水),纳多洛尔(18mg/kg/天,掺入大鼠饲料中),或比索洛尔(15mg/kg/天,溶于水)。治疗持续 36 天,然后大鼠接受 SD/对照暴露(1 周)。之后,进行焦虑样和抑郁样行为、社会互动和学习记忆功能测试。SD 大鼠表现出焦虑样和抑郁样行为以及学习记忆障碍。普萘洛尔和纳多洛尔可保护 SD 大鼠免受焦虑或抑郁样行为的发生。比索洛尔治疗不能减轻 SD 诱导的大鼠行为损伤。纳多洛尔、普萘洛尔或比索洛尔对减轻 SD 诱导的记忆功能测试没有影响。这些结果表明,某些“β-阻滞剂”有可能减轻创伤事件的负面心理影响。

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