Using a DNA microarray method to examine gene expression in brain from clozapine-injected mice.

After our 2002 report on the changes of gene expression in the brain from phencyclidine-treated mouse by using DNA microarray (Toyooka et al., Ann. N.Y. Acad. Sci. 965: 10-20), we decided to apply this DNA microarray method for the brain of the mouse treated with other drugs. We are now examining the effects of clozapine on the brain function. Clozapine is an atypical antipsychotic drug. Clozapine has affinity for neurotransmitter receptors, including D4 dopamine, serotonin, histamine, and adrenergic receptors. MacGibbon et al. (Mol. Brain Res. 23: 21-32) reported that clozapine and haloperidol produced a differential pattern of immediate early gene expression in rat caudate-putamen. Kobayashi et al. (Br. J. Pharmacol. 123: 421-426) have observed the effects of clozapine on the opioid receptors and G-protein-activated inwardly rectifying potassium channel of Xenopus oocytes. Thomas et al. (J. Neurochem. 76: 789-796) found that clozapine increases apolipoprotein D expression in the mouse brain. Therefore, we are going to apply this DNA microarray method to examine the effects of clozapine on mouse brain function. After we injected clozapine into mice for 20 days, we decapitated the mice. We then used the DNA microarray method to examine the gene expression of mouse brain. We found some changes in the mouse brain treated with clozapine. For example, the intensity of a potassium channel spot decreased, and that of a serotonin receptor spot increased.