Title:In Vivo Antidepressant Efficacy of 3-Substituted Thietane-1,1-dioxide Derivative - A Preliminary Study for Novel Anti-Depression Therapy in Neurological Disorders
Volume: 20
Issue: 10
Author(s): Irina L. Nikitina, Narasimha M. Beeraka, Gulnara G. Gaisina, Kirill V. Bulygin, Elmira F. Galimova, Shamil N. Galimov, Vladimir N. Nikolenko, Liudmila M. Mikhaleva, Siva G. Somasundaram, Cecil E. Kirkland, Marco Avila-Rodriguez and Gjumrakch Aliev*
Affiliation:
- 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
Keywords:
Resident-intruder test, CMSS, 3-substituted thietane-1, 1-dioxide, antidepressant, SD rats, aggression.
Abstract:
Background: 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.
Objectives: 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.
Methods: 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.
Results: 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.
Conclusion: Serendipitously, we observed the ameliorative capability of N-14 cotreatment to mitigate
depressive-behavioral symptoms in intruders.
