This award will support collaborative research in neurobiology between Dr. George Koob, Scripps Clinical and Research Foundation, La Jolla, California, and Professor Michel LeMoal, University of Bordeaux II, France. The objective of the proposed research is to study the role of the peptide neurotransmitter corticotronin releasing factor (CRF) as a primary mediator of the behavioral state of stress and the behavioral responses to stress in the central nervous system. Recent studies have shown that CRF liberated directly into the central nervous system may have neurotropic actions important for mobilizing behavioral responses to stress. The investigators have designed a set of experiments to identify the specific neural substrates for these behavioral actions by direct local interacerebral injection of CRF and CRF antagonists. In addition experiments are proposed to explore the possible mediation of these CRF effects via the central and peripheral noradrenergic systems. An attempt will be made to modify behavioral responses to CRF using specific pharmacological and neurotoxin induced inactivation of the central and peripheral noradrenergic systems. These studies have important implications for the role of pituitary peptides in brain function, and may provide important clues to the pathophysiology associated with behavioral disorders as diverse as depression, anxiety, and obesity. Over the past ten years Dr. Le Moal and his research group have developed and explored systematically behavioral and endocrine correlates of stress, coping and behavior. Dr. Koob's expertise is in classic behavioral pharmacology and basic neurobiology. The expected benefits to U.S. science from this project include not only the exchange of special behavioral techniques, but also the gain of valuable expertise regarding the measurement of brain function via behavioral techniques.