International Journal of Basic & Clinical Pharmacology | April 2020 | Vol 9 | Issue 4 Page 605 International Journal of Basic & Clinical Pharmacology Abbas A et al. Int J Basic Clin Pharmacol. 2020 Apr;9(4):605-610 http://www.ijbcp.com pISSN 2319-2003 | eISSN 2279-0780 Original Research Article An experimental study to evaluate the role of aspirin and metformin in prevention of depression in rats Alisha Abbas, Narendra Kumar*, Sarvesh Singh, Rahul Kumar, Akhlaque Ahmad, Rajendra Nath, Rakesh Kumar Dixit INTRODUCTION Major depressive disorder (MDD) is an extremely prevalent neuropsychiatric disease that affects around twenty five to thirty percent of the patients visiting out- patient departments. 1 Besides the disturbance in monoamine neurotransmitter system, the alteration in hypothalamic-pituitary-adrenal axis (HPA) is also an important contributing factor to the pathology of depression. 2 Increased activity of HPA axis leads to an increase in cortisol level which along with dysfunction of the central serotonergic system has a consequential effect on pathology of depression. 3 Several meta-analyses have gathered the colossal evidence, where pro-inflammatory markers like C reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor (TNF)-α have been found at increased levels among patients with depression which indicates that the immune system is closely associated with depression. 4,5 Inflammatory markers like IL-1β regulates the expression of the serotonin transporter gene and IL-6 may also contribute to the inhibition of proliferation. 6,7 This may be consistent with the hypothesis that hippocampal neurogenesis is necessary for the treatment of depression. It was also postulated that IL-6 can be utilised as a new Department of Pharmacology, King George Medical University, Lucknow, Uttar Pradesh, India Received: 22 January 2020 Accepted: 05 March 2020 *Correspondence: Dr. Narendra Kumar, Email: narenkgmu@gmail.com Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. ABSTRACT Background: Depression was seen to be associated with an increased level of inflammatory biomarkers along with the disturbance in the monoamine neurotransmitter system. Current therapies are mostly focussed on the neurotransmitters imbalance but due to increasing cases of treatment failure there is a need to shift our treatment focus to other potential therapies. This study aimed to evaluate the preventive role of aspirin and metformin in stress induced model of depression in wistar rats. Methods: Fifty four wistar rats were randomly divided into nine groups as normal control, experimental control, aspirin (30 mg/kg, 60 mg/kg), metformin (50 mg/kg, 100 mg/kg), two combination groups and imipramine (15 mg/kg). Depression model was created by the induction of chronic unpredictable mild stress (CUMS) for consecutive 28 days. Behavioural assessment was done by evaluating immobility time in forced swim test (FST) and sucrose preference ratio (SPR) in sucrose preference test. The data were analysed by analysis of variance (ANOVA) test using SPSS software. P<0.05 was considered to be statistically significant. Results: The CUMS led to an increase in immobility time and decrease in SPR. Aspirin and Metformin alone and their combinations showed statistically significant response in preventing the immobility time to increase (p<0.001) and SPR to decrease (p<0.001). However the response of Aspirin was comparable with Imipramine but the response of Metformin was not as significant as of Imipramine (p>0.05). Conclusions: Aspirin and metformin might have a potential role in the prevention of depression. Keywords: Aspirin, Chronic unpredictable mild stress, Depression, Inflammation, Metformin DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20201185