 The dopaminergic projections from the substantia nigra and the ventral tegmental area into the ventral striatum and medial prefrontal cortex mPFC play major roles in the neural processing underlying motivated behavior. Hypofunction of this system is hypothesized to underlie the anhedonia, psychomotor slowing and amotivation that characterize major depressive disorder MDD; Fibiger, 1991; Swerdlow and Koob, 1987. A variety of indirect evidence supports this hypothesis Wilner, 1995 as: 1 Cerebrospinal fluid CSF concentrations of the DA metabolite, homovanillic acid, are reduced in nondelusional, depressives. 2 Dextroamphetamine AMPH improves mood in depressed patients, and direct DA receptor agonists e.g. pramapaxil and DA reuptake inhibitors e.g. nomiphensine exert antidepressant effects. 3 Many somatic antidepressant therapies enhance D23 receptor sensitivity in limbic structures andor increase interstitial DA concentrations in the mPFC and accumbens in rats. 4 Conditions in which DA is depleted increase the risk for developing major depression, and DA receptor antagonist administration produces dysphoria, avolition and fatigue in healthy humans. 