Project Summary

Sang Ki Park, Ph.D (Young Investigator 2006) of Harvard Medical School, will use an animal model to study a modulator of the dopamine system and its role in mood disorders. Dopamine acts in target cells through five subtypes of dopamine receptors. Impairment in dopamine D2 receptor (D2DR) function is implicated in various psychiatric disorders. Thus, understanding the modulation of D2DR-mediated intracellular signaling could provide novel targets for treating various associated disorders. Dr. Park has proposed a prostate apoptosis response 4 (Par-4) as a novel modulator of dopamine signaling. A mouse lacking the D2DR interaction domain of Par-4, Par-4Δ LZ, exhibits impaired dopamine-CAMP-CREB signaling and increased depression-like behaviors. These observations imply Par-4 and D2DR interaction is critical for mood maintenance, and Par-4 function may be a therapeutic target for mood disorders. In this proposal, Dr. Park will further define details of Par-4-mediated modulation of D2DR signaling pathways. He also will evaluate the Par-4Δ LZ mouse as an model for mood disorders, examine Par-4 as an antidepressant therapeutic target, and develop a high-throughput screening for small molecules targeting Par-4.

Program Area: MOOD DISORDERS

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