OPPOSING ROLES FOR DOPAMINE AND SEROTONIN IN THE MODULATION OF HUMAN SPATIAL WORKING-MEMORY FUNCTIONS

Neurocognitive research has focused on monoaminergic influences over b road behavior patterns. For example, dopamine (DA) generally facilitat es informational transfer within limbic and cortical networks to promo te reward-seeking behavior. Specifically, DA activity in prefrontal co rtex modulates the ability for nonhuman primates and humans to perform spatial working memory tasks. Serotonin (5HT) constrains the activity of DA, resulting in an opposing relationship between DA and 5HT with respect to emotional and motor behaviors. A role for 5HT in constraini ng prefrontally guided spatial working memory (WM) processes in humans has not been empirically demonstrated but is a logical avenue for stu dy if these principles of neurotransmitter activity hold within cortic al networks. In this study, normal humans completed a visuospatial WM task under pharmacological challenge with (i) bromocriptine, a DA agon ist and (ii) fenfluramine, a serotonin agonist, in a double-blind, rep eated-measures, placebo-controlled design. Findings indicate that brom ocriptine facilitated spatial delayed, but not immediate, memory perfo rmance. Fenfluramine resulted in impaired delayed spatial memory. Thes e effects were not due to nonspecific arousal, attentional, sensorimot or or perceptual changes. These findings suggest that monoaminergic ne urotransmitters (DA and 5HT) may interact within cortical networks to modulate the expression of specific cognitive behaviors, particularly effortful processes associated with goal-directed activity.