Changes in gene expression can be maintained over the life of an organism and may underlie long term changes in addictive behavior. Abused drugs-induce long-term behavioral disorders that are thought to be maintained by biological mechanisms in the central nervous system that are largely unknown. Work in this group during previous FYs has developed approaches to identifying such genes and documented candidate genes whose expression are regulated by abused drugs, including amphetamine, cocaine and morphine, but represent novel sequences without homologs in genebank searches. One cDNA in this class of new genes was pursued. Screening of rat cortex cDNA libraries produced a 2.4 kb in cDNA that recognizes to a 8 kb mRNA in rat cerebral cortex. Further studies will assess the brain distribution of this gene product, its regulation with development and additional drug treatments, and other gene homologs of what now appears to represent a prototypic member of a novel, drug-regulated gene family.