This is an application for supplemental funding for a program-project grant for laboratory and human studies on the biochemical basis of opiate addiction, especially on endorphins and opiate receptors. The grant includes a core support element that funds general laboratory support as well as secretarial and computer services. There are four projects. The first project undertakes to apply a radioimmunoassay developed in our laboratory to measure beta-endorphin in blood plasma and cerebrospinal fluid of normals and chronic pain patients, patients receiving acupuncture, psychotic patients, and heroin addicts in methadone and naltrexone maintenance. The second project undertakes to continue work on characterizing the distribution and physiological role of dynorphin, an opiod peptide recently discovered in our laboratory. The third project is to study effects of chronic naloxone infusion in human volunteers, and also to examine the possibility that endorphins mediate placebo responses. The fourth project undertakes to elucidate the role of membrane lipids in the function of opiate receptors, following up discoveries in our laboratory concerning the inactivation of opiate receptors by lipid peroxidation. Although approved for renewal by the IRG, the grant suffered massive and crippling budget cuts that would have effectively destroyed its purpose. The present application is a detailed justification of our request that many (though not all) of these budget cuts be restored.
