Abused drugs produce long-lasting changes in behaviors via biochemical mechanisms that are largely unknown. Drug-altered changes in expression of specific genes in the brain can provide a major window on possible biochemical substrates for addiction. To further explore this area, we have established and developed subtracted differential display and array hybridization techniques that have allowed identification of dozens of distinct cDNAs that correspond to candidate drug-regulated genes expressed in brain. During this FY, we have enhanced characterization of candidate genes whose expression is regulated by amphetamine, cocaine and morphine. Sequence analyses of one of these cDNAs revealed novel splice variant isoforms of a cell adhesion gene family member, NrCAM. Studies of this gene's expression reveal that it is a good candidate to contribute to altered synaptic connectivities that could play roles in the complex neuroadaptive processes characteristic of addiction.