Preclinical study on cognitive and antidepressant effects of chronic low-dose olanzapine

Background Although in bipolar patients the main therapeutic indication of olanzapine (OLA) is the management of acute mania, several observations suggest that this agent may exert antidepressant as well as antimanic effects. However, in our knowledge, there are no preclinical studies supporting this hypothesis. Thus, the main goal of the present work was to evaluate the putative antidepressant effect of OLA (0.02–0.1 or 0.5 mg/kg/day), in comparison to amitriptyline (AMI) (5 mg/kg/day), haloperidol (HAL) (0.2 mg/kg/day) and sodium valproate (VPA) (5.0 or 30 mg/kg/day), in rats exposed to a protocol of chronic mild stress (CMS). The second aim of this project was to assess the efficacy of OLA, AMI, HAL and VPA in reverting the cognitive impairment produced by the anhedonic state. Both control and anhedonic rats will be subjected to two short-memory paradigms, the place recognition test and the object discrimination test, in order to evaluate the effects of the examined drugs on visuospatial memory.