p,p′-Methoxyl-diphenyl diselenide elicits an antidepressant-like effect in mice without discontinuation anxiety phenotype

•(MeOPhSe)2 single administration elicited an antidepressant-like effect.•(MeOPhSe)2 repeated administration elicited an antidepressant-like effect.•(MeOPhSe)2 repeated administration elicited an anxiolytic-like action.•(MeOPhSe)2 discontinuation did not cause anxiogenic-like effect.•(MeOPhSe)2 repeated administration caused neither renal nor hepatic toxicity.

Major depressive disorder is the most severe and debilitating disease among psychiatric illnesses. The abrupt interruption of antidepressant treatment may lead to a complex physiological and neuropsychiatric syndrome. The organoselenium compound (MeOPhSe)2 has been reported to have neuroprotective properties in animal models. The study aimed to investigate the effects of single or repeated administration of (MeOPhSe)2 on depressive-like behavior and if the compound administration, and its discontinuation, may affect the anxiolytic-like phenotype in Swiss mice. The results showed that repeated intragastric administration of (MeOPhSe)2 (dose range: 0.1-5 mg/kg), different from a single administration, reduced the immobility time in the mouse tail suspension test. A single administration of (MeOPhSe)2 at a dose of 5 mg/kg decreased the immobility time, increased the swimming time and did not alter the climbing behavior in the modified forced swimming test (mFST). Repeated administration of (MeOPhSe)2 decreased the immobility time, did not alter the swimming time and increased the climbing behavior in the mouse mFST. Repeated administration of (MeOPhSe)2 at a dose of 5 mg/kg elicited a mouse anxiolytic-like phenotype in the elevated plus maze and light-dark tests. Markers of hepatic and renal function tests were not altered by repeated administration of (MeOPhSe)2 to mice. The findings indicate that a single or repeated administration of (MeOPhSe)2 elicited an antidepressant-like action in mice. Moreover, repeated treatment with (MeOPhSe)2 produced an anxiolytic-like action in mice and its profile remained stable after discontinuation.