This is a request for Research Scientist Development Award (Level II). The purpose of applying for an RSDA is to allow for a change in the terms of Dr. Kellogg's present position from a major involvement in teaching to allow her full-time committment to research. The objectives of the proposal are to pursue to provocative findings that have been reported from her laboratory to date concerning the effect of psychotherapeutic drugs on the developing brain. Specifically, experiments are designed to probe mechanisms mediating the effect of developmental exposure to diazepam on the new approaches to bear on the problem, and the learning of these new techniques is part of Dr. Kellogg's plans for professional growth. Immunocytochemical analysis of the noradrenergic (NE) terminal distribution in the hypothalamus and of specific NE target cells will assist in determining whether subpopulations of NE projections and target cells are primarily affected. Dr. Kellogg will collaborate with Dr. Gloria Hoffmann in the Department of Neurobilogy and Anatomy in the execution of the experiments and in the learning of the techniques. Autoradiography of benzodiazepine binding will be carried out to determine the localization of binding in the hypothalamus during the critical exposure period and to correlate the binding with ingrowth of NE fibers to the region. The procedure for autoradiography is being developed with assistance from local investigators. As part of the plans for professional growth, however, Dr. Kellogg will spend time in Switzerland with Dr. Margaret Schlumpf who has conducted many studies on neuroreceptors in fetal brain. Other experiments are designed to determine possible molecular mechanisms that may have been influenced by the early exposure or mediate the effects; such as changes in calcium availability, the influence of adenylate cyclase systems and/or alterations in function of the benzodiazepine- GABA binding complex. To prepare for future directions, Dr. Kellogg plans to begin to develop molecular biologic approaches to analysis of the nervous system with assistance from Dr. Robert Angerer in the Department of Biology.
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