α-(phenylselanyl) acetophenone abolishes acute restraint stress induced-comorbid pain, depression and anxiety-related behaviors in mice.

ABSTRACT

α-(phenylselanyl) acetophenone (PSAP) is an organoselenium compound that presents antidepressive-like and antinociceptive effect in animal models. In this study, we evaluate the potential pharmacological effects of PSAP on acute stress restriction (ARS)-induced depressive and anxiogenic-like behavior associated with hyperalgesia and mechanical allodynia in male adult Swiss mice (25-35 g). The ARS is an unavoidable stress situation that was applied for a period of 4 h using an individual rodent restraint. Ten min after ARS, the animals were treated with the PSAP (10 mg/kg, intragastrically [IG]) or imipramine (IMI, 10 mg/kg, IG) and after thirty min they were submitted to the behavioral observations in the forced swimming test (FST), sucrose preference test, hot plate, Von-Frey Hair filaments (VHF), marble burying test and elevated plus maze (EPM). It was also evaluated the levels of plasma corticosterone and some parameters of oxidative stress in cortex and hippocampus. The ARS caused a decrease in the latency to the first episode of immobility in the FST, the sucrose preference, latency time in the hot plate test, frequency of paw withdrawal in the VFH and time spent in the open arms of the EPM. ARS also increased the immobility time of mice in the FST, the number of marbles buried and enclosed entries number in the EPM. PSAP or IMI reversed all these parameters. ARS increased the levels of lipid peroxidation, reactive species (RS) and nitrite and nitrate (NOx) levels in cortex and hippocampus and the treatment with PSAP or IMI also reduced these parameters, demonstrating its effect on the reduction of oxidative stress. In addition, ARS also caused an increase in plasma corticosterone levels and PSAP treatment reversed this effect. Hence, PSAP exhibited antidepressant-like, anxiolytic-like, anti-hyperalgesic and anti-allodynic effect in the ARS model and could be a promising molecule to treat these comorbidities.