ABSTRACT

Schizophrenia, is an important brain neurodevelopmental disorder observed in 1% of the global population. Classical antipsychotics cause extrapyramidal side effects and are less effective on the negative symptoms of schizophrenia. New-generation atypical antipsychotics have been developed as alternatives to typical antipsychotics for more effective on negative symptoms of schizophrenia such as mood and memory disorders or safer therapy. Olanzapine and clozapine are new atypical antipsychotics that are frequently used in clinics.

Effects of olanzapine and clozapine on depression and anxiety in the forced swimming (FST) and elevated plus maze (EPM) test were examined in mice. Since there is a growing interest in the role of neutrophins in the pathophysiology of schizophrenia, the effects drugs on the expression levels of brain neurotrophic factors (BDNF, CREB, NGF, synapsin and FGF2) in the hippocampus of mice were also investigated. Mice were treated chronically and intraperitoneally with olanzapine (1and 2 mg/kg,) or clozapine (1.25 and 2.5 mg/kg) for 10 days and 60 and 30 minutes respectively before FST and EPM tests on the 11^th day.

In the FST test, clozapine (2.5 mg/kg; p<0.05) significantly decreased immobility time while olanzapine (1ve 2 mg/kg; p>0.05) had no significant effect on this parameter. In the EPM test, olanzapin (2 mg/kg; p<0.01) and clozapine (1.25 ve 2.5 mg/kg; p<0.01 and p<0.05 respectively) significantly increased both % time spent in open arms (p<0.001) and % open arm entries (p<0.01). Clozapine up-regulated the expression of BDNF, CREB, NGF synapsin and FGF2 in the mice hippocampus. Olanzapine up-regulated the expression of NGF, synapsin and FGF2 but it down-regulated the expression of BDNF and CREB.

Clozapine seems to possess superior effects compared to olanzapine on negative semptoms of schizophrenia since it up-regulates more neurotrphic factors than olanzapine in the brain.

Keywords: Antipsychotics, behaviour, neurotrophic factors