Subtracted differential display: Genes with amphetamine-altered expression patterns include calcineurin

Genes whose expression changes with administration of abused substances provide candidate biochemical mechanisms for drug-induced long-term brain changes. To identify such genes, and to avoid the false positive results frequently obtained from differential display PCR, we applied a subtracted differential display (SDD) approach. We subtracted single-stranded cDNA prepared from drug-treated animals with excess mRNA from saline-treated animals, and visa versa, prior to differential display amplifications. Two of the initial amphetamine-regulated cDNAs identified in this fashion encoded calcineurin A, a neuron-specific protein phosphatase catalytic subunit whose striatal expression was upregulated ca. 1.5-fold. SDD may enhance the utility of differential display approaches to identifying regulated genes in tissues in which mRNA complexities are high.