EFFECT OF REPEATED CO-TREATMENT WITH <EM>N</EM>-ACETYLCYSTEINE AND ARIPIPRAZOLE ON THE NEURODEVELOPMENT RAT MODEL OF SCHIZOPHRENIA

Aims: Some clinical study have shown that the atypical antipsychotic drug aripiprazole, and the antioxidant N-acetylcysteine were effective in reducing positive and negative symptoms of schizophrenia in patients. The aim of the present study was to evaluate the influence of repeated co-treatment with aripiprazole and N-acetylcysteine on the schizophrenia-like behavior in adult rats.
Method: The schizophrenia-like behavior was induced in Sprague-Dawley male pups in the neonatal days (p5-p16) by repeated administration of the glutathione synthesis inhibitor L-butionine-(S,R)-sulfoximine (BSO). Adult rats were repeated co-treatment with aripiprazole (0.1 mg/kg) and N-acetylcysteine (10 mg/kg) for 21 days, and their effects on schizophrenia-like behavior were assessed (in p90-91) using the social interaction, novel object recognition test and mRNA BDNF level in some brain structures.
Results and Conclusions: The obtained data indicated that the studied drugs at higher doses: aripiprazole (0.3 mg/kg) and N-acetylcysteine (30 mg/kg) reversed schizophrenia-like symptoms in tested model. Moreover, repeated co-treatment at ineffective doses, aripiprazple (0.1 mg/kg) with N-acetylcysteine (10 mg/kg) also reversed schizophrenia-like behavior in the neurodevelopmental rat model of schizophrenia. The above results indicated that N-acetylcysteine enhances the action of aripiprazole in the used neurodevelopmental rat model of schizophrenia. Adding N-acetylcysteine to aripiprazole in the BSO model of schizophrenia leads for lowering the dose of this antipsychotic, which is crucial for therapy both negative symptoms and cognitive functions, and indicates the usefulness this model to study these symptoms.
Acknowledgment: This study was financially supported by statutory funds of the Maj Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.