Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, RS, Brazil.
Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, RS, Brazil.
Behav Brain Res. 2020 May 27;386:112602. doi: 10.1016/j.bbr.2020.112602. Epub 2020 Mar 14.
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.
抑郁症是一种以情绪和情感失衡为特征的严重障碍，伴随着单胺能信号的减少。单胺氧化酶抑制可导致大脑中单胺能神经递质水平升高。根据我们之前的研究，3-苯基-4-(苯硒基)异喹啉（PSI）是一种体外选择性和可逆的 MAO-B 抑制剂。本研究旨在研究单次 PSI 剂量对脑 MAO 活性的潜在体外抑制作用及其在小鼠强迫游泳试验（FST）中的抗抑郁样作用。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，PSI 溶解在菜籽油中，以确定时间进程（0.5-24 h）和剂量反应（25-100 mg/kg，10 ml/kg，灌胃）曲线，使用成年 C57Bl/6 雄性小鼠测定 MAO 活性抑制。单次 PSI 剂量 100 mg/kg 可抑制给药后 8 小时小鼠全脑 MAO-B 活性，但不改变 MAO-A 活性。FST 在 PSI 给药（100 mg/kg）或载体后 0.5、8 和 24 h 进行，但仅在治疗后 0.5 和 8 h 显示其抗抑郁样作用。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，单次 PSI 剂量 100 mg/kg 在 FST 后 0.5 和 8 h 对小鼠有抗抑郁样作用。此外，脑 MAO-B 活性抑制和多巴胺受体调节有助于 PSI 在小鼠中的抗抑郁样作用。
