Modification of spatial recognition memory and object discrimination after chronic administration of haloperidol, amitriptyline, sodium valproate or olanzapine in normal and anhedonic rats.

In the present study we have investigated the effects of a chronic administration of olanzapine (Ola) on visual and spatial memory in normal and anhedonic rats. The effects of Ola have been compared to those of the typical antipsychotic Hal, the tricyclic antidepressant amitriptyline (Ami), and the mood stabilizer VPA. Anhedonia (assessed by reduction of sucrose preference) was induced by administration of a chronic mild stress (CMS) protocol, in which rats were exposed sequentially, over a period of 4 wk, to a variety of unpredictable mild stressors. The spatial memory was evaluated by testing the ability of the rats to discriminate a familiar vs. a novel environment, while the visual memory was assessed by testing the ability of the rats to discriminate familiar vs. novel objects. In CMS-free rats, VPA (5 or 30 mg/kg.d), Ola (0.02 or 0.1 mg/kg.d), Ami (2 mg/kg.d) and Hal (0.2 mg/kg.d) caused no detectable modifications of visual memory, whereas VPA (5 mg/kg.d), Ami (2 mg/kg.d) and Ola (0.02 mg/kg.d) did not modify spatial memory performance. In our experimental conditions, the administration of the CMS protocol caused an impairment of both visual and spatial memory. The chronic treatment of anhedonic rats with Ola (0.02 mg/kg.d) or Ami (2 mg/kg.d) prevented, at least in part, the stress-induced impairment of visuospatial performance. In conclusion, the results of the present preclinical study seem to indicate that the chronic administration of low doses of Ola or Ami has the potential to lead to substantial cognitive benefits in depressed patients.