Transcription factors insolved in the development of drug abuse and therapeutic drugs.

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We have found that the activity of Purα, a single stranded DNA-binding protein, is changed with chronic morphine treatment. The DNA-binding activity was found to be enhanced by endogenous activator. The activator was purified and identified to be calmodulin (CaM) which enhanced the DNA-binding activity of Purα more than 10 times. CaMIII gene in three CaM genes was only activated by chronic morphine treatment. The enhancer activity of CRE/CREB and neurite outgrowth from PC12 cells were suppressed by Purα. These results suggest that Calcium signaling is involved in the gene expression by morphine.Arc, an immediate early gene is reported to be induced markedly by methamphetamine in the brain. Amida was isolated by yeast two hybrid system. Amida has two nuclear translation signals and transported to the nuclei and caused cell death. Arc formed a complex with Amida and transported to nuclei and suppressed apoptotic activity of Amida. Amida was phosporylated at serine-180 by Cdc2/cyclin B and changed the DNA-binding activity. The data suggest that the ratio of Amida and Arc is a critical factor for cell death during methamphetamine administration, which may cause the methamphetamine psychosis.