Viral-Mediated Gene Transfer

This involves the use of recombinant viruses to express a protein in a localized region of brain. We engineer herpes simplex virus (HSV) or adeno-associated virus (AAV) vectors to express the drug- or stress-regulated protein, or a dominant negative inhibitor of that protein. These viral vectors are injected into a brain reward region, where they infect only neurons and express the encoded protein in a highly circumscribed region of brain. By overexpressing the protein, and by expressing an inhibitor of the protein, it is possible to both mimic and block the drug- and stress-induced change. Viral-mediated gene transfer is used in both rats and mice.