Research Elucidates Mechanism by which Gene Expression may be Altered during Drug Addiction

Dr. Potashkin, Associate Professor and Vice Chair of the Department of Cellular and Molecular Pharmacology, is an expert in gene expression. She commented, “Addiction is a brain disorder that manifests itself by repetitive behaviors despite negative consequences.

Currently, there is an abundance of information known about the cellular and behavioral changes that occur during addiction, but little is understood concerning the changes that occur at the molecular level with regards to gene expression. Understanding the changes that occur between transcription and protein synthesis is key to revealing the mechanism that leads to addiction.”

Dr. Potashkin's studies focus on how the primary RNA transcript is processed by splicing to produce a mature transcript. The fidelity of splicing must be maintained since errors may lead to the development of disease. One immediate and prominent alteration that occurs with administration of amphetamine or cocaine is the accumulation in one region of the brain of very stable truncated isoform of the transcription factor FosB termed DFosB that is produced by alternative splicing of the transcript.

DFosB mediates some of the neural and behavioral modifications that occur with drug addiction. The results from the study identified a splicing factor, polypyrimidine tract binding protein, as a key factor in regulating the switch in splicing that result in the truncated form of FosB being produc ed instead of the less stable full-length protein. The study also provided clues about the signaling pathway that is activated that leads to splicing regulation. This information provides several potential therapeutic targets for drug addiction.