Behavioral sensitization can be initiated by repetitive stress or stimulant drug administration. Our laboratory has recently cloned and sequenced a glucocorticoid-induced receptor (GIR) cDNA from rat prefrontal cortex in a stress model of learned helplessness. The full-length GIR cDNA encodes a protein belonging to the G protein-coupled receptor superfamily, whose ligand is unknown. This protein shares 31 percent-34 percent amino acid identity to the tackykinin receptors NK-1, NK-2, NK-3. As regulation of neuronal gene expression is hypothesized to be one mechanism by which amphetamine leads to long-term behavioral sensitization, we propose to explore the relationship of GIR to the initiation or maintenance of sensitization. Our preliminary studies demonstrate that chronic amphetamine administration results in elevated expression of GIR in rat prefrontal cortex, which persists long-term (7 days) following drug discontinuing. These findings lead us to hypothesize that modulation of GIR expression may be involved in the physiological regulation and neuroadaptation in the addictive process. This proposal will determine the time-dependent and region-specific expression of GIR in rats sensitized to amphetamine, explore the cellular localization of GIR through in situ hybridization and immunocytochemistry, and generate a transgenic mouse model overexpressing rat GIR.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32DA014172-01
Application #
6340439
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Babecki, Beth
Project Start
2001-04-01
Project End
Budget Start
2001-04-01
Budget End
2002-03-31
Support Year
1
Fiscal Year
2001
Total Cost
$49,412
Indirect Cost
Name
Cincinnati Children's Hospital Medical Center
Department
Type
DUNS #
071284913
City
Cincinnati
State
OH
Country
United States
Zip Code
45229