Effects of diphenyl diselenide on behavioral and biochemical changes induced by amphetamine in mice.

Abstract

Diphenyl diselenide (PhSe)2, an organoselenium compound, has been studied as a potential pharmacological agent in different in vitro and in vivo models, mainly due to its antioxidant properties. However, there are few studies concerning the effects of (PhSe)2 on dopaminergic system. Thus, the purpose of the present study was to evaluate the effects of acute and sub-chronic treatment of (PhSe)2 on amphetamine-induced behavioral and biochemical parameters. In acute protocol, mice were pre-treated with 5 or 10 mg/kg of (PhSe)2 and 30 min after, amphetamine was administered. In sub-chronic protocol, mice were pre-treated with 5 or 10 mg/kg of (PhSe)2 during 7 days and 24 h after, amphetamine was administered. Twenty-five minutes after amphetamine administration, behavioral (crossing, rearing, time of stereotypy and immobility) and biochemical (MAO activity, DCFH-DA oxidation, protein and non-protein thiol groups) parameters were analyzed. Amphetamine increased the number of crossing and rearing and (PhSe)2 prevented only the increase in the number of crossings when acutely administered to mice. Furthermore, amphetamine increased stereotypy and time of immobility in mice. (PhSe)2, at 10 mg/kg, increased per se the stereotypy and time of immobility when sub-chronically administered. (PhSe)2, at 10 mg/kg, potentiated the stereotypy caused by amphetamine in both protocols. Sub-chronic treatment with (PhSe)2 either alone (5 and 10 mg/kg) or in combination (10 mg/kg) with amphetamine decreased brain MAO-B activity. Oxidative stress parameters were not modified by (PhSe)2 and/or amphetamine treatments. In conclusion, sub-chronic administration of (PhSe)2 can promote a behavioral sensitization that seems to be, at least in part, dependent of MAO-B inhibition.