This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Major depressive disorder (MDD) is a common, recurrent, and disabling disorder. Despite a wide range of antidepressant treatments available, MDD remains difficult to treat. Therefore, a better understanding of treatment mechanisms and identification of reliable predictors of treatment response would constitute major progress in the battle against MDD (e.g., Pizzagalli et al., 2001 for a recent example). Wellbutrin XL (active drug: bupropion hydrochloride), is an effective, FDA-approved antidepressant treatment. Although bupropion is assumed to inhibit the neuronal uptake of dopamine (DA), a neurotransmitter implicated in brain reward mechanisms, its precise mechanisms of action are unknown. As an initial step toward a better understanding of the mechanism of action of bupropion in humans, this application proposes a double-blind, placebo-controlled, single-dose neuroimaging study to investigate the effects of acute bupropion administration on neural activity underlying reward processing and hedonic capacity in MDD and healthy volunteers. A greater understanding of the biochemistry of the brain's reward system will lead to a greater ability to treat dysfunctions of the reward system such as anhedonia, a lack of pleasure in normally enjoyable activities, which occurs in such various psychiatric disorders as schizophrenia, major depression, and substance dependence (Willner 2000).
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