Dependence upon central nervous stimulants, including both illicit (e.g., cocaine, methamphetamine) and licit (amphetamine-based medications, e.g., Adderall(c)) psychostimulants, constitutes a serious health problem in the U.S. Not only has abuse of illicit stimulants increased at an alarming rate in the past few years, the use and diversion of prescription stimulants is also on the rise. However, no biomarker or panel of biomarkers is available to assist in diagnosis of stages or progression of stimulant abuse and dependence in the general population. Using a rodent self-administration model, we propose experiments to test the hypothesis that a specific gene expression signature in blood can serve as a diagnostic biomarker that distinguishes control from drug treated animals. Illumina bead microarrays will be used to obtain expression profiles from blood samples at several stages of self-administration of stimulants and drug-naive rats. The discovery of biomarkers with sensitivity, specificity, and predictive power would be a great diagnostic advance and the development of such diagnostic tools would benefit from large-scale analyses to identify disease-specific molecular markers that provide a fingerprint of the condition. Two Specific Aims are proposed: 1) identify a panel of candidate biomarkers (genes) in rat whole blood samples that predicts early and late phases of cocaine self- administration as well as early and late stages of forced abstinence from cocaine, 2) validate candidate biomarkers and correlate with brain gene expression in rat stimulant self-administration as well as early and late stages of forced abstinence (withdrawal). We will test the hypothesis that expression based markers can accurately distinguish between stages of cocaine self-administration and forced abstinence and the same stages following methamphetamine self-administration. PUBLIC HEALTH RELEVANCE: This application will use gene expression profiling in whole blood to identify candidate biomarkers indicative of psychomotor stimulant abuse (cocaine and methamphetamine). Discovery of reliable biomarkers could lead to new drug treatments;and, a molecular screening test for abuse holds promise for treatment and intervention of the disease.