It has been well established that upon repeated exposure to drugs of abuse profound long-term neurochemical changes in specific brain regions occur, an effect that may be partially mediated by alterations in gene expression. One way to examine the drug-induced adaptations in the brain is by identifying transcription factors sensitive to drugs of abuse. Chronic Fras, members of the FosB gene, are transcription factors induced following administration of various addictive substances, including morphine. It is thought that chronic Fra expression following repeated drug exposure plays a role in mediating long-term changes in the brain by altering the expression of other genes. Given the potential role of the chronic Fras in the regulation of long-lasting alterations in the brain, it is important to understand the mechanism by which chronic Fras are induced after opiate administration. We hypothesize that D1 dopamine receptors are involved in the modulation of chronic Fras by morphine. Therefore, the experiments outlined below will investigate whether D1 dopamine receptors mediate morphine-induced chronic Fra upregulation, and, in addition, identify the downstream intracellular signaling molecules such as PKA and MAPK/ERK which may be involved in chronic Fra over-expression by morphine.
| Muller, Daniella L; Unterwald, Ellen M (2005) D1 dopamine receptors modulate deltaFosB induction in rat striatum after intermittent morphine administration. J Pharmacol Exp Ther 314:148-54 |
| Muller, Daniella L; Unterwald, Ellen M (2004) In vivo regulation of extracellular signal-regulated protein kinase (ERK) and protein kinase B (Akt) phosphorylation by acute and chronic morphine. J Pharmacol Exp Ther 310:774-82 |
