Compromised glutathione-dependent redox system of chronically-isolated rats: a harmful side effect of clozapine

Abstract

Changes in glutathione (GSH)-related systems are implicated in depressive disorders. Since chronic psychosocial stress contributes to depression, we investigated the effects of 21d of chronic social isolation (CSIS) stress, an animal model of depression, as well as chronic administration of clozapine, an atypical antipsychotic, on GSH content, glutathione peroxidase (GPx) and glutathione reductase (GLR) in the prefrontal cortex of rats. Increased GPx protein expression and its activity in clozapine-treated (controls or chronically-isolated) rats as well as in CSIS group were found. Nonetheless, clozapine administration caused decrease in GSH content but no effects on GLR in controls and CSIS group. Data indicate that CSIS compromises GSH-dependent redox system promoting oxidative stress in rat prefrontal cortex which can’t be protected by clozapine. Moreover, clozapine administration in controls has a harmful side effect on this redox system.