The effects of donepezil on phencyclidine-induced cognitive deficits in a mouse model of schizophrenia.

Abstract

Donepezil is the first-line of treatment for Alzheimer's disease (AD), which improves cognitive impairment effectively, but whether it has an impact on cognitive impairment in schizophrenia remains unknown. In this study, we evaluated the effects and mechanisms of donepezil on schizophrenia-like cognitive deficits induced by phencyclidine (PCP). The cognitive deficits model of schizophrenia was established by injecting PCP into mice. Risperidone, an atypical antipsychotic drug, served as positive control drug. Three behavioral tests including novel object recognition (NOR) test, Morris Water Maze (MWM) and passive avoidance (PA) test were performed to evaluate the effect of donepezil on PCP-induced cognitive deficits. Furthermore, the content of BDNF and NGF in the hippocampus and cortex of mice was determined using ELISA. Expressions of p-GSK-3β/GSK-3β, p-Akt/Akt, Bcl-2/Bax and Caspase-3 in the hippocampus and cortex were detected by Western blot. Results revealed that donepezil has a protective effect on PCP-induced cognitive dysfunction. Moreover, donepezil can also improve PCP-induced schizophrenia-like cognitive deficits by inhibiting neuronal apoptosis and regulating synaptic plasticity, which was possible through the up-regulation of p-Akt, p-GSK-3β, Bcl-2 and the down-regulation of Bax, Caspase-3. The results indicated that donepezil might exhibit a beneficial effect on the treatment of cognitive dysfunction in schizophrenia.