The National Institute on Drug Abuse desires new methods to localize and chemically characterize neuropeptide interactions in the CNS in response to drugs of abuse. The objective of the proposed research is to develop the new technology of imaging mass spectrometry (IMS) to directly obtain spatial maps of peptides present in particular brain regions. IMS produces images of a brain slice or tissue with a mass spectrum obtained at each point. This technology is based on matrix-assisted laser desorption/ionization (MALDI) mass spectrometry and can obtain ten micron spatial resolution and ten thousand mass resolution from a biological sample. Using IMS, neuropeptides are measured without preselection so that large numbers of peptides can be studied simultaneously, thus making possible the interactions between classical transmitters and a great diversity of neuropeptides to be followed. A modification of the technology will allow neuropeptide release from precisely controlled regions to be measured under different stimulation paradigms. Both the spatial imaging and peptide release studies will be used to detect changes in neuropeptides as a function of drug exposure in rats to determine both changes in their expression level and distribution. This technology development ideally matches the cutting-edge basic research award solicitation. By developing powerful new proteomics-based technologies to answer questions about the most complex and elusive set of neuromodulators, and neuropeptides, basic insight into the effects of drugs of abuse on the CNS will be gained.
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