The role of atypical antipsychotics as add-on treatments and as primary mood stabilizers in different phases of bipolar disorder is an important current research area. Although in bipolar patients the main therapeutic indication of quetiapine (QTP) 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 QTP (0.4, 2.0, or 10 mg/kg/day), in comparison to amitriptyline (AMI) (2 or 5 mg/kg/day), in rats exposed to acute or chronic stress. The administration of QTP, 2 mg/kg/day, prevents the onset of anhedonia in rats exposed to a 6-week chronic mild stress (CMS) protocol. The effect of QTP has a slow onset, beginning at week 5, and causes a complete recovery from anhedonia. In this respect, the effect of QTP is similar to that obtained after chronic administration of AMI 2 or 5 mg/kg/day. Our findings also indicate that a 6-week administration of QTP, 2 or 10 mg/kg/day, has protective effects against the onset of anhedonia caused by the exposure to an acute subthreshold stressful event in rats that have previously experienced the CMS procedure. The results suggest that QTP is able to prevent both the transient mood depression caused by acute stress and the long-lasting anhedonic state induced by exposure, over a period of weeks, to a variety of unpredictable mild stressors.

Although in bipolar patients the main therapeutic indication of atypical antipsychotics is the management of acute mania, several observations suggest that these agents may exert antidepressant as well as anti-manic effects. The main goal of the present work was to evaluate the putative antidepressant effect of chronic olanzapine (Ola) (0.02-0.1 or 0.5 mg/kg.d), in comparison to haloperidol (Hal) (0.2 mg/kg.d) and sodium valproate (VPA) (5 or 30 mg/kg.d), in rats exposed to a protocol of chronic mild stress. The tricyclic compound amitriptyline (Ami) (5 mg/kg.d) was used as reference drug. The results indicate that Ola, in a rodent model of depression, has protective effects against the stress-induced anhedonia. Compared to Hal and VPA, Ola shows a greater antidepressant activity and is as effective as Ami in preventing the anhedonic state. The effects of Ola and Ami, however, have a different time-course. A full reversion of the anhedonia by Ami appears after a latency of 4 wk, whereas the effect of Ola is already evident 1 wk after the beginning of the chronic treatment. Moreover, the recovery from anhedonia at the end of the stress protocol and after drug cessation was more rapid in groups of rats pretreated with Ola or VPA than in the group of saline-pretreated rats. In conclusion, the results indicate that 0.02 mg/kg.d Ola causes a rapid and sustained antidepressant-like effect, while all other anti-manic treatments show loss of efficacy at 3 wk. Taken together, these observations support the hypothesis that Ola has a broader pharmacotherapeutic profile than solely as an antipsychotic or anti-manic agent.

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.

INTRODUCTIONThe term canine cognitive dysfunction syndrome (CCDS) is used in veterinary literature to describe the progressive neurodegenerative disorder of senior dogs that is characterized by a gradual decline in cognitive function [1,2]. Currently a diagnosis of cognitive impairment is based on identifying the clinical symptoms by collecting owner's opinions and observations. Although neuropsychological testing is certainly a better measure of cognitive impairment than owner assessment, most of the pet dogs are periodically controlled by veterinary practitioners that are not specialists of behaviour. Since this condition does not allow the use of complex procedures, availability to practitioners of a battery of easy and short protocols to measure the cognitive impairment is advisable. In the present work we have developed a battery of tests (open field, curiosity test and reversal learning) for assessment of cognitive decline in pet dogs.

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