Oliveira Mayara Cecile Nascimento, Cavalcante Ikla Lima, de Araújo Alana Natalícia, Ferreira Dos Santos Aline Matilde, de Menezes Renata Priscila Barros, Herrera-Acevedo Chonny, Ferreira de Sousa Natália, de Souza Aquino Jailane, Barbosa-Filho José Maria, de Castro Ricardo Dias, Almeida Reinaldo Nóbrega, Scotti Luciana, Scotti Marcus Tullius, Da Silva Stiebbe Salvadori Mirian Graciela
Laboratory of Psychopharmacology, Institute for Research in Drugs and Medicines, Federal University of Paraíba, João Pessoa 58051-900, PB, Brazil.
Laboratory of Cheminformatics, Institute for Research in Drugs and Medicines, Federal University of Paraíba, João Pessoa 58051-900, PB, Brazil.
Pharmaceuticals (Basel). 2023 Oct 4;16(10):1408. doi: 10.3390/ph16101408.
Major depressive disorder is a severe mood disorder characterized by different emotions and feelings. This study investigated the antidepressant activity of the phenylpropanoid methyleugenol (ME) in adult female mice exposed to a stress model induced by dexamethasone. The animals were randomly divided into groups containing eight animals and were pre-administered with dexamethasone (64 μg/kg subcutaneously). After 165 and 180 min, they were treated with ME (25, 50 and 100 mg/kg intraperitoneally) or imipramine (10 mg/kg intraperitoneally) after 45 min and 30 min, respectively; they were then submitted to tests which were filmed. The videos were analyzed blindly. In the tail suspension test, ME (50 mg/kg) increased latency and reduced immobility time. In the splash test, ME (50 mg/kg) decreased grooming latency and increased grooming time. In the open field, there was no statistical difference for the ME groups regarding the number of crosses, and ME (50 mg/kg) increased the number of rearing and time spent in the center. Regarding in silico studies, ME interacted with dopaminergic D1 and α1 adrenergic pathway receptors and with tryptophan hydroxylase inhibitor. In the in vivo evaluation of the pathways of action, the antidepressant potential of ME (50 mg/kg) was reversed by SCH23390 (4 mg/kg intraperitoneally) dopaminergic D1 receptor, Prazosin (1 mg/kg intraperitoneally) α1 adrenergic receptor, and PCPA (4 mg/kg intraperitoneally) tryptophan hydroxylase inhibitor. Our findings indicate that ME did not alter with the locomotor activity of the animals and shows antidepressant activity in female mice with the participation of the D1, α1 and serotonergic systems.
重度抑郁症是一种以不同情绪和情感为特征的严重情绪障碍。本研究调查了苯丙素类化合物甲基丁香酚（ME）对成年雌性小鼠在由地塞米松诱导的应激模型中的抗抑郁活性。将动物随机分为每组八只的组，并预先皮下注射地塞米松（64μg/kg）。在165分钟和180分钟后，分别在45分钟和30分钟后用ME（25、50和100mg/kg腹腔注射）或丙咪嗪（10mg/kg腹腔注射）处理；然后让它们接受拍摄测试。对视频进行盲法分析。在悬尾试验中，ME（50mg/kg）增加了潜伏期并减少了不动时间。在喷水试验中，ME（50mg/kg）减少了梳理潜伏期并增加了梳理时间。在旷场试验中，ME组在穿越次数方面没有统计学差异，而ME（50mg/kg）增加了直立次数和在中央区域花费的时间。关于计算机模拟研究，ME与多巴胺能D1和α1肾上腺素能途径受体以及色氨酸羟化酶抑制剂相互作用。在体内作用途径评估中，ME（50mg/kg）的抗抑郁潜力被SCH23390（4mg/kg腹腔注射）多巴胺能D1受体、哌唑嗪（1mg/kg腹腔注射）α1肾上腺素能受体和对氯苯丙氨酸（4mg/kg腹腔注射）色氨酸羟化酶抑制剂所逆转。我们的研究结果表明，ME不会改变动物的运动活性，并在D1、α1和5-羟色胺能系统参与下在雌性小鼠中显示出抗抑郁活性。
