The proposed research will continue ongoing studies of the physiological actions of the monoamines DA (dopamine) and NE (norepinephrine), on the function of neural circuits in the CNS. In this phase of research, we aim to study the activity of neural circuits in dorsal and ventral neostriatum during behaviors leading to cocaine self-administration. Newly developed methodology will allow arrays of (multiple microwires to be implanted in dorsal and ventral neostriatum to obtain long-term recordings of ensembles of single neuron spike trains. Rats will be trained to press a bar for cocaine IV self-administration under a variety of experimental conditions. Rats will also locomote after cocaine administration and recordings of the same ensemble of neurons across different behavioral states. Nucleus accumbens neurons will be studied in selected cases across free behaviors during a 24-hour cycle. The anatomical distribution of behaviorally specific activity will be mapped in detail in n. accumbens and caudate-putamen in relation to the topography of afferents, efferents and the patch-matrix organization as defined by naloxone binding sites. Ensemble recording will be carried out in SI-MI cerebral cortex and dorsolateral neostriatum to determine influences of cocaine on the cerebrostriatal system. A search will be made in medial prefrontal cortex and other regions afferent to n. accumbens for the origin of anticipatory activity found to precede bar press for drug selfadministration. Chronic recordings also will be made in anterior lobe and ventral paraflocculus of cerebellum to assess possible cocaine actions via facilitation of the cerebellum NE-system. Correlations will be made between results obtained the known modulatory actions of cocaine, DA, and NE as revealed in previous cellular studies and also in future parallel studies of modulatory actions of these monoamines.
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