Velasquez Daniela, Quines Caroline, Pistóia Renan, Zeni Gilson, Nogueira Cristina W
Laboratory of Synthesis, Reactivity, Pharmacological and Toxicological Evaluation of Organochalcogen Compounds, Department of Biochemistry and Molecular Biology, Center of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS 97105-900, Brazil.
Laboratory of Synthesis, Reactivity, Pharmacological and Toxicological Evaluation of Organochalcogen Compounds, Department of Biochemistry and Molecular Biology, Center of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS 97105-900, Brazil.
Physiol Behav. 2017 Mar 1;170:100-105. doi: 10.1016/j.physbeh.2016.12.024. Epub 2016 Dec 21.
Depression is a leading cause of disability worldwide. For this reason, the aim of this study was to investigate the possible antidepressant-like activity of 2-benzoyl-4-iodoselenophene (CHIOSe), a selenophene compound, in two well-consolidated behavioral assays for screening antidepressant activity (forced swimming test and tail suspension test) in mice. In order to investigate the mechanism of action of CHIOSe, it was investigated the activities of cerebral enzymes: monoamine oxidase MAO A and B and Na, K ATPase, and if an inhibitor of serotonin synthesis, p-chlorophenylalanine (pCPA) (100mg/kg) blocks the antidepressant-like effect of CHIOSe. Swiss mice received (CHIOSe) (5-50mg/kg) or canola oil by the intragastric (i.g.) route before behavioral tests. The results showed that CHIOSe at dose range of 5-50mg/kg decreased immobility time in the tail suspension test. In the forced swimming test, CHIOSe reduced the immobility time at the doses of 10 and 50mg/kg. CHIOSe differently affected the cerebral cortical Na, K ATPase; the effects on this enzyme were dependent of the dose tested. At a dose of 10mg/kg, the compound increased Na, K ATPase activity, while the activity was inhibited at a dose of 50mg/kg. pCPA blocked the antidepressant-like action of CHIOSe in mice. Therefore, CHIOSe (5-50mg/kg) selectively inhibited MAO-A activity in cerebral cortices of mice. The modulation of serotonergic system contributed to the antidepressant-like action of CHIOSe in mice.
抑郁症是全球导致残疾的主要原因。因此，本研究的目的是在两项成熟的用于筛选小鼠抗抑郁活性的行为学试验（强迫游泳试验和悬尾试验）中，研究硒吩化合物2-苯甲酰基-4-碘硒吩（CHIOSe）可能的抗抑郁样活性。为了研究CHIOSe的作用机制，研究了脑酶的活性：单胺氧化酶MAO A和B以及钠钾ATP酶，以及血清素合成抑制剂对氯苯丙氨酸（pCPA）（100mg/kg）是否会阻断CHIOSe的抗抑郁样作用。在行为学试验前，瑞士小鼠通过灌胃（i.g.）途径接受（CHIOSe）（5-50mg/kg）或菜籽油。结果表明，在5-50mg/kg剂量范围内的CHIOSe减少了悬尾试验中的不动时间。在强迫游泳试验中，CHIOSe在10和50mg/kg剂量下减少了不动时间。CHIOSe对大脑皮层钠钾ATP酶有不同影响；对该酶的影响取决于所测试的剂量。在10mg/kg剂量下，该化合物增加了钠钾ATP酶的活性，而在50mg/kg剂量下活性受到抑制。pCPA阻断了CHIOSe在小鼠中的抗抑郁样作用。因此，CHIOSe（5-50mg/kg）选择性抑制了小鼠大脑皮层中的MAO-A活性。血清素能系统的调节促成了CHIOSe在小鼠中的抗抑郁样作用。
