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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31DA017421-01
Application #
6738571
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Babecki, Beth
Project Start
2003-09-17
Project End
2005-05-16
Budget Start
2003-09-17
Budget End
2004-09-16
Support Year
1
Fiscal Year
2003
Total Cost
$27,954
Indirect Cost
Name
Temple University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
057123192
City
Philadelphia
State
PA
Country
United States
Zip Code
19122