The research described in this proposal is intended to investigate the mechanism(s) of action of opiate drugs and cocaine in the central nervous systems of rodents. We will use electrophysiological techniques to characterize the direct and indirect actions of these drugs in various brain regions in in vitro brain slices, single and double in oculo brain grafts, in situ in acutely anaesthetized preparations, and in unanaesthetized chronically implanted animals. We will measure electrophysiological responses with intracellular recording techniques, and with extracellular recording of spontaneous unit activity and evoked field responses. Our primary hypothesis is that animals self-administer these drugs because of some reinforcing aspect of drug administration, and that such reinforcement depends upon a monoaminergic substrate in the central nervous system. Therefore, we will attempt to determine whether opiate drugs such as morphine and cocaine appear to have a common electrophysiological action on this putative monoamine """"""""reward"""""""" system which might provide a basis for their common neuropharmacological actions. In terms of long-range objectives, we hope to define the mechanisms of action of opiates and cocaine in reinforcement-related systems, as opposed to their actions in other neuronal systems (e.g., those involved in analgesia, etc.). If we can establish that these drugs have a common mechanism of action in a particular brain region, or in relation to a specific neurotransmitter, then we would have a basis for predicting the abuse potential of drugs based upon some pharmacological criterion. Ultimately, this might lead to a better understanding of the phenomenon of drug abuse in general, and in particular what kinds of biological bases which might underlie individual differences in the use of abused drugs.
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