Psychostimulants and opiates are known to induce behavioral dependence syndromes that are presumed to be mediated by corresponding long-term changes in the central nervous system. Alterations in protein synthesis and/or gene expression are strong candidate mechanisms to play roles in these processes. Work in this laboratory during previous FYs has documented that psychostimulants and opiates can modify the expression of several DNA-binding transcription factors in specific brain regions. However, which genes are regulated by those transcription factors remain largely unknown. Differential display following polymerase chain reaction amplification (PCR-DD) provides a powerful new tool to identify such genes whose expression levels are altered by drugs. During this FY, we have identified interesting candidate genes for involvement in dependence mechanisms through this approach.