Project Summary

Brian A. Baldo, Ph.D. (Young Investigator 2002) of University of Wisconsin, Madison, will investigate orexin/hypocretin, a peptide that has been found to play a key role in the central modulation of arousal and feeding.  The orexin/hypocretin system is involved in mediating two behavioral processes known to be perturbed in depression, arousal and feeding, and receives strong input from the two monoamine neuromodulators most strongly implicated in depression, norepinephrine and serotonin.  Dr. Baldo will examine the role of the orexin/hypocretin system in modulating the positive motivational state engendered by rewarding electrical stimulation of the lateral hypothalamus, and the anatomical substrates underlying this potential modulation.  He will also explore the ability of the noradrenergic and serotonergic drugs to activate orexin/hypocretin-containing neurons, and chronic antidepressant treatments to modulate orexin/hypocretin gene expression.  These experiments will add to the knowledge of the neural substrates underlying depression, and potentially identify a novel direction for the development of future antidepressant drugs targeting the hypothalamic orexin/hypocretin system.

Program Area: MOOD DISORDERS\Depression (Unipolar)

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