J Cogn Neurosci. 1992 Winter;4(1):58-68. doi: 10.1162/jocn.1992.4.1.58.
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.
最近关于认知神经生物学的研究集中在前额叶皮层（PFC）支持工作记忆过程的能力上，即通过暂时维持与正确反应相关的信息，以便在逐个试验的基础上重新评估或更新的记忆过程。最近最感兴趣的是多巴胺（DA）在 PFC 主沟区域的空间工作记忆过程中所起的作用。虽然 D1 DA 受体似乎调节了猴子的这些记忆过程，但有几条研究线索表明 D2 DA 受体也可能与认知功能有关。因此，我们评估了一种特定的 D2 受体激动剂（溴隐亭）和安慰剂对人类被试者视觉空间延迟反应表现的影响。在 0 秒或 8 秒的延迟期间，被试者需要记住在 360°圆周内的外周视觉中快速呈现的视觉线索的空间位置。通过溴隐亭激活 D2 受体相对于安慰剂表现，评估 D2 受体激活在 8 秒延迟条件下对工作记忆的促进程度。作为溴隐亭 D2 受体作用的验证手段，确定了催乳素（PRL）分泌的最大抑制，PRL 分泌是通过 D2 受体部位的激活特异性抑制的。此外，还进行了没有工作记忆成分的任务，以排除溴隐亭对感觉、觉醒、注意力和运动因素的非特异性影响。结果表明，溴隐亭对空间延迟反应表现有显著的促进作用（即 8 秒延迟表现）。结果不能用溴隐亭的非特异性作用来解释。因此，这项研究的结果表明，空间工作记忆是通过 D2 受体激活来促进的。在 DA 在促进目标导向行为中的一般作用的更大理论框架内，讨论了 DA 在人类认知过程中可能起的作用。在认知的情况下，DA 可能促进有助于通过复杂环境引导动机行为的过程。
