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α-(phenylselanyl) acetophenone abolishes acute restraint stress induced-comorbid pain, depression and anxiety-related behaviors in mice
Neurochemistry international ( IF 4.2 ) Pub Date : 2018-08-13 , DOI: 10.1016/j.neuint.2018.08.006
Fernanda Severo Sabedra Sousa , Paloma Taborda Birmann , Renata Balaguez , Diego Alves , César Augusto Brüning , Lucielli Savegnago

α-(phenylselanyl) acetophenone (PSAP) is an organoselenium compound that presents antidepressive-like and antinociceptive effect in animal models. In this study, we evaluate the potential pharmacological effects of PSAP on acute stress restriction (ARS)-induced depressive and anxiogenic-like behavior associated with hyperalgesia and mechanical allodynia in male adult Swiss mice (25–35 g). The ARS is an unavoidable stress situation that was applied for a period of 4 h using an individual rodent restraint. Ten min after ARS, the animals were treated with the PSAP (10 mg/kg, intragastrically [IG]) or imipramine (IMI, 10 mg/kg, IG) and after thirty min they were submitted to the behavioral observations in the forced swimming test (FST), sucrose preference test, hot plate, Von-Frey Hair filaments (VHF), marble burying test and elevated plus maze (EPM). It was also evaluated the levels of plasma corticosterone and some parameters of oxidative stress in cortex and hippocampus. The ARS caused a decrease in the latency to the first episode of immobility in the FST, the sucrose preference, latency time in the hot plate test, frequency of paw withdrawal in the VFH and time spent in the open arms of the EPM. ARS also increased the immobility time of mice in the FST, the number of marbles buried and enclosed entries number in the EPM. PSAP or IMI reversed all these parameters. ARS increased the levels of lipid peroxidation, reactive species (RS) and nitrite and nitrate (NOx) levels in cortex and hippocampus and the treatment with PSAP or IMI also reduced these parameters, demonstrating its effect on the reduction of oxidative stress. In addition, ARS also caused an increase in plasma corticosterone levels and PSAP treatment reversed this effect. Hence, PSAP exhibited antidepressant-like, anxiolytic-like, anti-hyperalgesic and anti-allodynic effect in the ARS model and could be a promising molecule to treat these comorbidities.



中文翻译:

α-(苯硒基)苯乙酮消除了小鼠的急性束缚应激诱发的并发疼痛,抑郁和焦虑相关行为

α-(苯硒基)苯乙酮(PSAP)是一种有机硒化合物,在动物模型中具有抗抑郁样和抗伤害感受的作用。在这项研究中,我们评估了雄性成年瑞士小鼠(25-35 g)对急性应激限制(ARS)引起的与痛觉过敏和机械性异常性疼痛相关的抑郁和焦虑症行为的PSAP的潜在药理作用。ARS是不可避免的压力情况,使用单独的啮齿动物约束器施加了4小时。ARS后十分钟,对动物进行PSAP(10 mg / kg,胃内[IG])或丙咪嗪(IMI,10 mg / kg,IG)的治疗,三十分钟后将其接受强迫游泳的行为观察测试(FST),蔗糖偏爱测试,热板,冯弗雷发丝(VHF),大理石掩埋测试和高架迷宫(EPM)。还评估了皮质和海马中血浆皮质酮的水平以及氧化应激的一些参数。ARS导致FST的第一动不动的潜伏期缩短,蔗糖偏爱,热板试验的潜伏期时间,VFH中爪子缩回的频率以及在EPM张开臂上花费的时间减少。ARS还增加了FST中小鼠的固定时间,EPM中埋藏的大理石数量和封闭的入口数量。PSAP或IMI颠倒了所有这些参数。ARS可增加脂质过氧化,反应性物质(RS)以及亚硝酸盐和硝酸盐(NO 蔗糖偏好,热板测试中的潜伏时间,VFH中爪子缩回的频率以及EPM张开双臂所花费的时间。ARS还增加了FST中小鼠的固定时间,EPM中埋藏的大理石数量和封闭的入口数量。PSAP或IMI颠倒了所有这些参数。ARS可增加脂质过氧化,反应性物质(RS)以及亚硝酸盐和硝酸盐(NO 蔗糖偏好,热板测试中的潜伏时间,VFH中爪子缩回的频率以及EPM张开双臂所花费的时间。ARS还增加了FST中小鼠的固定时间,EPM中埋藏的大理石数量和封闭的入口数量。PSAP或IMI颠倒了所有这些参数。ARS可增加脂质过氧化,反应性物质(RS)以及亚硝酸盐和硝酸盐(NOx)在皮质和海马中的水平以及PSAP或IMI的治疗也降低了这些参数,证明了其对减少氧化应激的作用。此外,ARS还引起血浆皮质酮水平升高,PSAP治疗逆转了这种作用。因此,PSAP在ARS模型中表现出抗抑郁样,抗焦虑样,抗痛觉过敏和抗痛觉过敏作用,并且可能是治疗这些合并症的有前途的分子。

更新日期:2018-08-13
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