The aim of this project is to improve the understanding of the role of brain noradrenergic systems, represented by the nucleus locus coeruleus, in emotion and behavior. Previous research has supported the idea that part of the function of the noradrenergic systems may be relevant to human anxiety and to the mode of action of several major classes of anxiolytic drugs, including the benzodiazepines, tricyclic antidepressants, monoamine oxidase inhibitors, beta-adrenergic blockers, opiates, and others. The methods of study include neurophysiologic, neuropharmacologic, and biochemical techniques to test the hypothesis that the locus coeruleus is associated, at least in part, with anxiety or fear. The hypothesis will be tested by investigating two corollaries which are derived from it: (a) that acute inactivation of the locus coeruleus should diminish or prevent behavioral effects which are associated with its activation and with fear, and (b) that fear-inducing stimuli should increase and effective anxiolytic drugs should reduce, these same behaviors and the firing rates of individual locus coeruleus neurons. Central noradrenergic activity will also be studied during the same or similar conditions using measurements of the concentrations of the norepinephrine (NE) metabolite 3-methoxy 4-hydroxy phenylethylene glycol (MHPG) in venous blood, a technique which might be applicable to human clinical studies as well. 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 different directions. 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 of the neural mechanisms of normal anxiety and the etiology and treatment of pathological anxiety, anxiety disorders, and possibly other stress-related clinical problems.
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