Department of Pharmacology, Clinical Pharmacology, Bashkir State Medical University, Lenina Street, 3, Ufa 450008, Russian Federation.
I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), 8/2 Trubetskaya Str., Moscow 119991, Russian Federation.
CNS Neurol Disord Drug Targets. 2021;20(10):982-995. doi: 10.2174/1871527320666210301115028.
Psychosocial stress-induced depressive behavior is linked to the etiology of several neurological diseases viz., PTSD, and neurodegenerative disease like Alzheimer's Disease (AD). The repeated bouts of social stress defeat can be induced using Resident-Intruder- Paradigm (RIP) and Chronic Mild Social Stress (CMSS) animal models to assess the stress-induced depressive behavioral patterns.
The aim of this study to examine the anti-depressive efficacy of 3-methoxythietane- 1,1-dioxide (N-14) in RIP models of behavioral alterations.
In this study, we have used Sprague-Dawley rats in Resident-Intruder-Paradigm (RIP), where intruders interacted with residents Day 0 to Day +5 for 10 minutes to invoke CMSS in intruders and became defeated/submissive rats due to the depressive-like behavioral alterations in social activity, explorations, grooming, defense, aggressive behavior, social interaction, freeze, rearing etc., with residents. Control intact animals are included in group I, group II received N-14 alone; group III received CMSS, and group IV received cotreatment of N14 with CMSS. N-14 (2 mg/kg) was administered intraperitoneally from Day 0 to Day +5 to intact animals and intruder animals under conditions of CMSS.
Several behavioral tests viz., forced swim test, open field test, and elevated-plus maze test were used to examine the above behavioral dynamic parameters. The dynamic interaction between Residents and Intruders during the study showed substantial alterations in exploratory activity, aggressiveness, defensive behavior, body weight, and thymus mass in stressed animals. N-14 cotreatment has mitigated sociability, exploratory activity, aggressiveness increased social adaptability and defensive behavior. An extensive rise in active forms of defense and submission latency indicates that N-14 has induced antidepressant activity with a psycho-sedative component of action.
Serendipitously, we observed the ameliorative capability of N-14 cotreatment to mitigate depressive-behavioral symptoms in intruders.
心理社会应激诱导的抑郁行为与几种神经疾病的病因有关，例如创伤后应激障碍和阿尔茨海默病等神经退行性疾病。可以使用“居民-入侵者范式（RIP）”和“慢性轻度社会应激（CMSS）”动物模型来反复诱发社交挫败，以评估应激诱导的抑郁行为模式。
本研究旨在研究 3-甲硫基噻吩-1,1-二氧化物（N-14）在 RIP 行为改变模型中的抗抑郁作用。
在这项研究中，我们使用 Sprague-Dawley 大鼠进行“居民-入侵者范式（RIP）”，入侵者在第 0 天到第+5 天与居民每天互动 10 分钟，以在入侵者中引起 CMSS，并由于社交活动、探索、梳理、防御、攻击行为、社交互动、冻结、站立等方面的抑郁样行为改变而变得沮丧/顺从的老鼠，与居民在一起。将完整的对照动物包括在第 I 组中，第 II 组单独接受 N-14；第 III 组接受 CMSS，第 IV 组接受 N14 与 CMSS 的联合治疗。从第 0 天到第+5 天，将 N-14（2mg/kg）腹膜内注射到完整动物和 CMSS 条件下的入侵者动物中。
多项行为测试，如强迫游泳测试、旷场测试和高架十字迷宫测试，用于检查上述行为动态参数。研究期间居民和入侵者之间的动态相互作用显示，应激动物的探索活动、攻击性、防御行为、体重和胸腺质量发生了实质性变化。N-14 联合治疗减轻了社交能力、探索活动、攻击性、增加了社会适应性和防御行为。积极防御形式的广泛增加和屈服潜伏期表明，N-14 具有抗抑郁作用，具有行为作用的心理镇静成分。
我们偶然观察到 N-14 联合治疗对减轻入侵者抑郁行为症状的改善能力。
