Keywords
Abstract
The aim of the study was to evaluate the effect of dapagliflozin and empagliflozin, inhibitors of sodium-glucose cotransporter type 2 (SGLT2), on the emotional stress response of intact animals in an open field test, on anxiety, depressive behaviour, memory, physical endurance, and pain of various origins. The experiments have been carried out on outbred white mice. Antidiabetic drugs of the SGLT2 inhibitor group dapagliflozin (50 mg/kg) and empagliflozin (20 mg/kg) were administered into the stomach as a suspension of crushed tablets over 30–40 min before testing. Psychotropic effects were investigated in the open field test, elevated plus maze, hanging mice by tail, passive avoidance test, and swimming with load test. To study the effect on the central component of pain sensitivity, the «Hot plate» test was used, and on the peripheral component, the «Acetic writhing» test was used. Dapagliflozin and especially empagliflozin reduce depressive behavior in the tail suspension test. Empagliflozin also shows nootropic properties by improving memory in the passive avoidance test. Both SGLT2 inhibitors did not significantly affect anxiety in the elevated plus maze test and the behaviour of mice in the open field test (a tendentious increase in exploratory activity in the open field test under the influence of empagliflozin generally corresponds to the stimulating action of the drug). Both drugs do not increase physical endurance in the swimming with load test. Dapagliflozin, but not empagliflozin, render an analgesic effect in the «Hot Plate» test, suggesting a central mechanism of analgesic action. In the «Acetic writhing» test, both drugs showed no effect, which indicates the absence of their distinct peripheral component of analgesic activity. Thus, SGLT2 inhibitors have pleiotropic properties. Empagliflozin is characterized by a stimulating effect on the central nervous system, has antidepressant and nootropic effects, which may be useful for affective and cognitive disorders correction, and dapagliflozin, due to its central analgesic properties, can be considered as a promising agent for correction of pain syndromes in diabetes mellitus.