The long-term objective of this research is to understand the specific role played by catecholamines (CA) in information processing by the central nervous system. The proposed research will focus in large part on: i) the role of the CA projections to the intermediolateral cell column of the spinal cord (IML) (nucleus of orgin of the sympathetic preganglionic neurons, SPN's) and on ii) the mechanism of central Alpha-2 adrenergic postsynaptic inhibition (as it is presumably involved in the IML and possibly in the effects of the commonly used antihypertensive drugs clonidine and Alpha methyl DOPA). The nature and origin of these CA projections as well as the type of synaptic contacts established with the SPN's or the surrounding neuropil will be studied in the rat with neuroanatomical techniques combined with specific lesions. The effect of the various catecholamines on SPN's discharges will be studied with single-unit recordings and iontophoresis in the cat to examine the type of CA receptors involved in their action. In order to determine whether E or NE neurons are involved or not in the baroceptor reflex single unit recordings will be obtained from these neurons (C1 and A5) in the rat and the effect of pharmacologically induced alterations in blood pressure on their discharges will be investigated. For the same purpose an attempt will be made to determine the release of NE in the IML of the cat by voltammetry """"""""in vivo"""""""" and its modification by changes in peripheral blood pressure. Finally a tissue slice preparation of the pontine area (species to be determined) will be set up to study with intracellular techniques the mechanism of Alpha-2 mediated postsynaptic inhibition in the locus coeruleus. These experiments will contribute to further our understanding of the control by the CNS of the sympathetic outflow and of the mechanism of action of Alpha-2 adrenergic agonists.
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