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Dopaminergic system contribution to the antidepressant-like effect of 3-phenyl-4-(phenylseleno) isoquinoline in mice
Behavioural Brain Research ( IF 2.7 ) Pub Date : 2020-03-14 , DOI: 10.1016/j.bbr.2020.112602
Tuane Bazanella Sampaio 1 , Filipe Neimaier Bilheri 1 , Gilson Rogério Zeni 1 , Cristina Wayne Nogueira 1
Affiliation  

Depression is a serious disorder characterized by imbalance of mood and emotions, which is accompanied by the reduction in the monoaminergic signaling. The monoamine oxidase inhibition could lead to an increase in monoaminergic neurotransmitter levels in the brain. According to our previous study, 3-phenyl-4-(phenylseleno) isoquinoline (PSI) is a selective and reversible MAO-B inhibitor in vitro. The present study investigated the putative ex vivo inhibitory effect of a single PSI dose on the cerebral MAO activity and its antidepressant-like action in the mouse forced swimming test (FST). Additionally, the dopaminergic system contribution to the antidepressant-like effect of PSI was also evaluated. For this, PSI was dissolved in canola oil to determine time-course (0.5 – 24 h) and dose-response (25 – 100 mg/Kg, 10 ml/Kg, intragastrically) curves of MAO activity inhibition using adult C57Bl/6 male mice. A single PSI dose of 100 mg/Kg inhibited the MAO-B activity in the whole brain 8 h after administration to mice, while it did not alter the MAO-A activity. The FST was carried out 0.5, 8, and 24 h after the PSI administration (100 mg/Kg) or vehicle, but its antidepressant-like effect was demonstrated only at 0.5 and 8 h after treatment. Lastly, the contribution of dopaminergic system in the PSI antidepressant-like effect was demonstrated by using dopamine receptors antagonists, SCH23390, haloperidol and sulpiride. Thus, a single PSI dose of 100 mg/Kg had an antidepressant-like effect in mice subjected to the FST 0.5 and 8 h after its administration. Moreover, the inhibition of cerebral MAO-B activity and modulation of dopamine receptors contributed to the antidepressant-like effect of PSI in mice.



中文翻译:

多巴胺能系统对 3-苯基-4-(苯基硒基)异喹啉在小鼠中的抗抑郁样作用的贡献

抑郁症是一种以情绪和情绪失衡为特征的严重疾病,伴随着单胺能信号的减少。单胺氧化酶抑制可能导致大脑中单胺能神经递质水平的增加。根据我们之前的研究,3-phenyl-4-(phenylseleno)isoquinoline (PSI) 是一种选择性和可逆的体外MAO-B 抑制剂。本研究调查了推定的离体在小鼠强迫游泳试验 (FST) 中,单一 PSI 剂量对脑 MAO 活性及其抗抑郁样作用的抑制作用。此外,还评估了多巴胺能系统对 PSI 抗抑郁样作用的贡献。为此,将 PSI 溶解在菜籽油中,以确定使用成年 C57Bl/6 男性的 MAO 活性抑制的时间过程(0.5 – 24 小时)和剂量反应(25 – 100 毫克/公斤,10 毫升/公斤,胃内)曲线老鼠。给予小鼠 8 小时后,单剂量 100 mg/Kg 的 PSI 抑制了全脑中的 MAO-B 活性,而它没有改变 MAO-A 活性。FST 在 PSI 给药 (100 mg/Kg) 或载体后 0.5、8 和 24 小时进行,但其抗抑郁样作用仅在治疗后 0.5 和 8 小时显示。最后,通过使用多巴胺受体拮抗剂、SCH23390、氟哌啶醇和舒必利,证明了多巴胺能系统在 PSI 抗抑郁样作用中的贡献。因此,在给药后 0.5 和 8 小时接受 FST 的小鼠中,100 mg/Kg 的单一 PSI 剂量具有抗抑郁样作用。此外,大脑 MAO-B 活性的抑制和多巴胺受体的调节有助于 PSI 在小鼠中的抗抑郁样作用。

更新日期:2020-03-16
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