Kirk Wilhelmsen Michael F. Miles, M.D., Ph.D. Scientific Research Chronic use of addictive drugs causes behavioral adaptations that represent forms of CNS plasticity. Our laboratory studies the hypothesis that step-wise changes in gene expression, affecting synaptic activity or organization of brain reward pathways, contributes to CNS plasticity occurring with drug abuse. Our studies employ expression profiling with high density oligonucleotide arrays, a massively parallel method for studying gene expression on a near-genomic level. Identification of expression patterns contributing to addiction might generate novel targets for therapeutic agents and enhance our understanding of mechanisms underlying experience-dependent CNS plasticity.
Sensitization increases the rewarding properties of addictive drugs.
These expression patterns suggest functional changes that could contribute to increased dopamine release seen in nucleus accumbens with cocaine sensitization. Array studies, in combination with pharmacological, genetic and biochemical approaches, are currently being used to functionally link the regulation of specific genes to behavior of sensitization. We are studying patterns of gene regulation following acute ethanol exposure that correlate with long-term behavioral responses. Studies to date have identified a prominent role of prefrontal cortex in acute responses to ethanol. The gene expression patterns suggest several distinct targets of ethanol action.