1. ¹Institute of Medical Sciences, Tzu-Chi University, Hualien City, Taiwan
2. ²Department of Psychiatry, Tzu-Chi University and General Hospital, Hualien City, Taiwan

Correspondence: Dr C-H Chen, Department of Psychiatry, Tzu-Chi General Hospital, 707 Sec. 3 Chung-Yan Road, Hualien City 970, Taiwan. Tel: +886 3 8565301 ext.7539; Fax: +886 3 8461799; E-mail: cchen@mail.tcu.edu.tw

Received 26 April 2004; Revised 1 September 2004; Accepted 5 October 2004; Published online 10 November 2004.

Abstract

Long-term administration of antipsychotic drugs can induce differential expression of a variety of genes in the brain, which may underscore the molecular mechanism of the clinical efficacy and/or side effects of antipsychotic drugs. We used cDNA microarray analysis to screen differentially expressed genes in rat frontal cortex under 4 weeks' treatment of risperidone (1 mg/kg). Using real-time quantitative PCR, we were able to verify eight genes, whose expression were significantly upregulated in rat frontal cortex under chronic risperidone treatment when compared with control animals. These genes include receptor for activated protein kinase C, amida, cathepsin D, calpain 2, calcium-independent receptor for -latrotoxin, monoamine oxidase B, polyubiquitin, and kinesin light chain. In view of the physiological function of these genes, the results of our study suggest that chronic risperidone treatment may affect the neurotransmission, synaptic plasticity, and proteolysis of brain cells. This study also demonstrates that cDNA mciroarray analysis is useful for uncovering genes that are regulated by chronic antipsychotic drugs treatment, which may help bring new insight into the molecular mechanism of antipsychotic drugs.