Opposing roles for dopamine and serotonin in the modulation of human spatial working memory functions

Neurocognitive research has focused on monoaminergic influences over broadbehavior patterns. For example, dopamine (DA) generally facilitatesinformational transfer within limbic and cortical networks to promotereward-seeking behavior. Specifically, DA activity in prefrontal cortexmodulates the ability for nonhuman primates and humans to perform spatialworking memory tasks. Serotonin (5HT) constrains the activity of DA,resulting in an opposing relationship between DA and 5HT with respect toemotional and motor behaviors. A role for 5HT in constraining prefrontallyguided spatial working memory (WM) processes in humans has not beenempirically demonstrated but is a logical avenue for study if theseprinciples of neurotransmitter activity hold within cortical networks. Inthis study, normal humans completed a visuospatial WM task underpharmacological challenge with (i) bromocriptine, a DA agonist and (ii)fenfluramine, a serotonin agonist, in a double-blind, repeated-measures,placebo-controlled design. Findings indicate that bromocriptine facilitatedspatial delayed, but not immediate, memory performance. Fenfluramineresulted in impaired delayed spatial memory. These effects were not due tononspecific arousal, attentional, sensorimotor or perceptual changes. Thesefindings suggest that monoaminergic neurotransmitters (DA and 5HT) mayinteract within cortical networks to modulate the expression of specificcognitive behaviors, particularly effortful processes associated withgoal-directed activity.