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Abstract
Grant Number: 1R21DA017665-01 Project Title: Peptidomics of Cocaine and Amphetamine Abuse
PI Information: Name Title FRICKER, LLOYD D. fricker@aecom.yu.edu PROFESSOR Abstract: DESCRIPTION (provided by applicant): Proteomics methods provide a non-biased way of detecting and quantitating proteins and peptides, without prior knowledge of the particular protein or peptide. However, typical proteomics schemes detect only the most abundant proteins in a given tissue. While changes in these abundant molecules can be important in understanding the consequence of drug abuse, it is also important to examine the less abundant molecules such as those involved in signal transmission between cells. We have developed a novel method to selectively isolate peptide processing intermediates from fat/fat mouse brain, and have modified this method to permit the quantitation of relative levels of the peptides in two different groups of animals by differential isotopic labeling. The peptides isolated by this technique are substrates of carboxypeptidase E, an important enzyme in the biosynthesis of numerous neuroendocrine peptides. In Aim 1, we will use our quantitative peptidomics method to examine the effect of cocaine or methamphetarnine administration on the relative levels of peptides in specific brain areas such as the hippocampus, striatum, prefrontal cortex, and hypothalamus. Aim 2 will test whether any peptides found to be altered by the chronic cocaine or methamphetamine in the fat mice are similarly altered in wild type mice. Because the peptidomics technique cannot detect neuropeptides in wild type mice due to the high background from other molecules, this Aim will use traditional techniques such as radioimmunoassay and Northern blot analysis to examine peptide and mRNA levels. Taken together, these studies will provide a better understanding of the regulation of neuropeptides, both known and novel, in drug abuse.
Public Health Relevance:
This Public Health Relevance is not available.Thesaurus Terms:
brain, cocaine, drug abuse, methamphetamine, neuropeptide, peptide structure, proteomics
biological signal transduction, messenger RNA, protein quantitation /detection
biotechnology, laboratory mouse, liquid chromatography mass spectrometry, northern blotting, nucleic acid probe, radioimmunoassay, radiotracer, wild animal
Institution: ALBERT EINSTEIN COL OF MED YESHIVA UNIV 1300 Morris Park Avenue BRONX, NY 10461 Fiscal Year: 2004 Department: MOLECULAR PHARMACOLOGY Project Start: 01-MAR-2004 Project End: 28-FEB-2006 ICD: NATIONAL INSTITUTE ON DRUG ABUSE IRG: ZDA1