Antidepressant Activity of SGLT – 2 Inhibitors in Albinomice, an Experimental Study

Abstract

ObjectiveTo evaluate the antidepressant activity of SGLT-2 inhibitors in mice. MethodsSixty adult Swiss albino mice weighing 25-30 grams were selected. Thirty were allocated to forced swim test and thirty to tail suspension test models. In each model, there were 4 groups. The control group received vehicle (10 ml/kg, p. o) as standard, Imipramine (10 mg/kg, p. o) and the two test groups received dapagliflozin and capagliflozon respectively1hour prior to the acute study. In chronic study, the drugs were given orally once a day for 10 days and the last dose was given 1hour before the experiment. Duration of immobility was noted in forced swim test and tail suspension test.Statistical analysis was performed using Mean +/-SEM. ANOVA followed by Dunnett's test. P< 0.05 was considered statically significant. Results SGLT-2 inhibitors produced a significant antidepressant effect at all the doses, as indicated by the reduction in the duration of immobility compared to the standard. The antidepressant effect was higher with dapagliflozin when compared to capagliflozon and control. Conclusions SGLT-2 inhibitors has shown significant antidepressant activity greater than imipramine in mice.They have received considerable attention in recent times due to their beneficial effects on multiple physiological systems. After the realization of pleiotropic effects of SGLT-2 inhibitors 2 , they are being prescribed to patients suffering from cardiovascular disorders like hypertension and ischemic heart disease, irrespective of the lipid profile. SGLT-2 inhibitors are the most commonly prescribed in the world for chronic diabetic resistant patients for insulin .3 Glucose reduction using SGLT-2 inhibitors improves memory in some cases but not others. Controversy exists overuse of SGLT-2 inhibitors to alleviate memory problems in Alzheimer's disease (AD). 4 Correlations of glucose and cognitive function are mixed and association studies find that some genetic polymorphisms are related to cognitive function but others are not. 5Recently, some concerns are raised regarding effects of SGLT-2 inhibitors on memory and psychomotor functions.Hyperglycemia is thus suggested to partly mediate age-related brain changes. A Possible link between hyperglycemia and depression has been suggested in both clinical and preclinical studies. The recently proposed entity of vascular depression provides indirect support for hyperglycemia as a risk factor in the path physiology of depression. Since diabetes is more prevalent in geriatric patients, use SGLT-2 inhibitors may have beneficial effects on depression. Hence this study was undertaken to find out its role in animal models of depression. MATERIALS AND METHODSThe experimental protocol was approved by the Institutional Animal Ethics Committee (IAEC) of Chettinad Hospitals and Research Institute, Chettinad University, Chennai, India. Adult male Swiss albino mice weighing 25-35 gm from our breeding stock were used in this study. The animals were housed at 24±2 o C with 12:12 h light and dark cycle.They had...

Comparing sodium-glucose cotransporter 2 inhibitors and dipeptidyl peptidase-4 inhibitors on new-onset depression: a propensity score-matched study in Hong Kong

“…While early case reports suggested a potential association between incretin-based therapies and depression [11,12], recent cohort studies have found that DPP4I use is generally associated with a reduced risk of depression [13][14][15][16]. This is confirmed by clinical findings that DPP4 enzymatic activity is increased in patients with depressive symptoms [17] as well as pre-clinical findings in rodent model that DPP4I use produces antidepressant effects [18,19]. By contrast, there is limited data available to assess the anti-depressant effects of SGLT2I.…”