Strelow_2023_Prog.Neuropsychopharmacol.Biol.Psychiatry_125_110772

Synthetic glucocorticoid administration has been reported to play a role in depression and cognitive decline. The present study investigated the 2-phenyl-3-(phenylselanyl)benzofuran (SeBZF1) effects against the depressive-like behavior, memory impairment, and neurochemical alterations caused by acute dexamethasone administration in female Swiss mice. A dexamethasone dose-response curve (0.07-0.5 mg/kg, subcutaneous route, s.c.) was initially performed to validate the depressive-like behavior induction, in which the 0.25 mg/kg dose was more effective. Two experimental sets were performed to test the SeBZF1 (5 and 50 mg/kg, intragastric route, i.g.) pharmacological effect in this animal model. The 1st set revealed that the SeBZF1 reverses the dexamethasone-induced depressive-like behavior in the tail suspension test and in the splash test. In the 2nd experimental set, the compound effects of reversing the depressive-like behavior in the forced swimming test and the memory deficit in the Y-maze test induced by acute treatment with dexamethasone were demonstrated. Furthermore, SeBZF1 reversed the increase in the monoamine oxidase (MAO) activity in the prefrontal cortex (isoforms A and B) and in the hypothalamus (isoform A) caused by dexamethasone. However, no changes were observed in hippocampal MAO activity. Furthermore, animals treated with dexamethasone and SeBZF1 demonstrated a partially lower acetylcholinesterase activity in the prefrontal cortex compared with the induced group. In summary, the present study demonstrated that SeBZF1 reverses depressive-like behavior and memory deficits caused by acute dexamethasone treatment in female Swiss mice. Possibly the compound exerts its antidepressant-like action by increasing the availability of monoamines, while its effects on memory are still partially understood.