DRUGS OF ABUSE STUDIED THROUGH CHICK BRAIN MEMORY SYS

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The main aims are (1) to develop and test a chick learning system for behavioral-pharmacological-neurochemical studies of effects an mechanisms of opioids, and (2) to use this system to elucidat actions of opioids in the CNS in relation to learning and memory in order to increase understanding of the mechanisms of drug abuse. Chicks 1-3 days posthatch have many advantages for such research, but to date few studies have reported effects of opioids on learning and memory in th chick. Finding more precisely how opioids affect learning and memory would be valuable in itself and also as a model for the development of dependence on opiates. Specific lines of research to be undertaken in parallel are the following: 1. Analyze major anatomical regions of chick brain for several main opioids and for opioid receptors; i.e., use high performance liquid chromatography to analyze major metabolic products of the 3 parent opioid molecules, and use radioligands that are highly selective for the 3 major types of opioid receptors. The results will help to guide and interpret behavioral-pharmacological experiments using opioid agents with chicks (2 below). 2. Test opioids of the 3 main classes for amnestic effectiveness at certain brain sites, and investigate which stage(s) of memory formation are affected by amnestic opioids of the 3 main classes. Choice of opioid agents will be determined in part by those known to be effective in mammals and in part by our mapping of opioids and opioid receptors (1 above). 3. Investigate the neurochemical actions and time courses for some opioids found to be effective amnestic agents. As a major focus, test the dependence of LTM formation on protein synthesis by using an in vitro approach: test whether opioid amnestic agents reduce significantly the synthesis of proteins that are induced by one-trial training in the chick. We hypothesize that the brain measurements will closely parallel the behavioral end points, i.e., the opioid agents, given under appropriate conditions to produce amnesia, will significantly reduce the normal training- induced increase in synthesis of proteins. Also, determine the half-life of major opioids in chick brain; compare these with time- effect curves of these opioids on memory to see how they are related and to better understand the mechanisms involved. This project is based on a combination of mehods and expertise of the PIs with one-trial discrimination learning in the chick, opioids and opioid systems in behavioral experiments, and neurochemical techniques to study mechanisms of memory formation and of opioid effects.