The aim of this project is to improve the understanding of the role of brain noradrenergic systems, represented by the nucleus locus coeruleus (LC), on the behavior of monkeys. Our previous research, and extensive data of others, has supported the idea that part of the function of NE systems may be relevant to human anxiety and to the mode of action of anxiolytic drugs. The method of study will be to utilize the most specific neurophysiologic, neuropharmacologic, and biochemical techniques available to test the general hypothesis that the locus coeruleus is associated, at least in part, with anxiety or fear. This hypothesis will be tested by investigating two corollaries which are derived from it: (a) that activation of the locus coeruleus should produce behavioral evidence of fear or anxiety, which can be tested for noradrenergic pharmacological specificity, for similarities with environmentally elicited fear, and for reduction by anti-fear or anti-anxiety drugs, and (b) that fear-inducing stimuli should increase locus coeruleus activity as measured by concentrations of the norepinephrine metabolite MHPG in cerebral venous outflow and by increases in the firing rates of individual locus coeruleus neurons. Each of the techniques to be used will provide basic information about the functioning of the largest brain noradrenergic system, as well as test the principal hypothesis from a different direction. The use of nonhuman primates in these studies will make the results and some of the methods to be developed more relevant to humans because of extensive behavioral and monoamine system similarities between the primate species. The long-term goal is to improve the understanding and treatment of human anxiety.
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