The neuropeptide Y (NPY) signaling system is both structurally and functionally conserved between Drosophila and mammals. Recent studies from this laboratory have shown that Drosophila neuropeptide F (NPF), the single NPY homologue in the fly genome, plays important roles in modulating motivational feeding, locomotion and alcohol response. Parallel phenotypes have been observed between NPF-deficient flies and NPY-knockout mice: both animals displayed normal baseline feeding but deficits in motivational feeding; NPF-deficient fly larvae showed food-elicited hyperactive locomotion whereas NPY knockouts exhibited increased susceptibility to seizure; both NPF-deficient flies and NPY knockout mice displayed decreased ethanol sensitivity. Moreover, flies overexpressing NPF showed increased sensitivity to ethanol sedation, similar to the phenotypes of NPY-overexpressing mice. These observations strongly suggest that Drosophila is a suitable genetic model for the study of the neural, cellular and molecular mechanisms underlying the action the NPF/NPY signaling system. ? This proposed research aims to further elucidate the neurobiological basis of. NPY-mediated regulation of ethanol related behaviors.
The specific aims of this application include: 1) Identification and functional analysis of the neuroanatomical sites of the NPF system involved in modulation of ethanol response; 2) EMS-mutagenesis screen of genes involved in NPF/NPFR1-mediated ethanol response; 3) gain-of-function screen for genes involved in NPF/NPFR1 -mediated ethanol response.. The results from these studies should provide novel insights into understanding why a common neural signaling system underlies the controls of feeding and alcohol related behaviors, what components of the signaling pathway are conserved, and how genetic factors contribute to ethanol sensitivity in diverse organisms ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
1R01AA014348-01A2
Application #
6870408
Study Section
Neurotoxicology and Alcohol Study Section (NAL)
Program Officer
Neuhold, Lisa
Project Start
2005-02-01
Project End
2010-01-31
Budget Start
2005-02-01
Budget End
2006-01-31
Support Year
1
Fiscal Year
2005
Total Cost
$257,600
Indirect Cost
Name
University of Georgia
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
004315578
City
Athens
State
GA
Country
United States
Zip Code
30602