Facilitation of Working Memory in Humans by a D2 Dopamine Receptor Agonist

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Abstract
Recent studies on the neurobiology of cognition have focused on the ability of the prefrontal cortex (PFC) to support processes of working memory, i.e, mnemonic processes by which information relevant for a correct response is temporarily maintained to be reevaluated or updated on a trial-by-trial basis. Of most recent interest is the role played by dopamine (DA) in spatial working memory processes of the principal sulcal region of the PFC. Although D1 DA receptors appear to modulate these mnemonic processes in monkeys, several lines of research suggest that D2 DA receptors could also be relevant to cognitive functions. Therefore, we assessed the effects of a specific D2 receptor agonist (bromocriptine) and placebo on visuospatial delayed response performance in human subjects. During delay periods of 0 or 8 sec, subjects were required to remember the spatial location of rapidly presented visual cues displayed in peripheral vision within a 360° circumference. The extent to which D2 receptor activation by bromocriptine facilitated working memory in the 8–sec delay condition relative to placebo performance was assessed. As a means of providing validation of bromocriptine's D2 receptor effect, maximum inhibition of prolactin (PRL) secretion, which is inhibited specifically by activation of D2 receptor sites, was determined. Additionally, tasks having no working memory component were administered to rule out nonspecific effects of bromocriptine on sensory, arousal, attentional, and motor factors. Results demonstrated a significant facilitatory effect of bromocriptine on spatial delayed response performance (i.e., 8–sec delay performance). Results could not be explained by nonspecific effects of bromocriptine. Thus, findings of this study suggest that spatial working memory is facilitated by D2 receptor activation. The role that DA may play in human cognitive processes is discussed within the larger theoretical framework of DA's general role in the facilitation of goal-directed behavior. In the case of cognition, DA may facilitate processes that serve to guide motivated behavior through complex environments.