Müller U, von Cramon D Y, Pollmann S
Max-Planck-Institute of Cognitive Neuroscience, 04103 Leipzig, Germany.
J Neurosci. 1998 Apr 1;18(7):2720-8. doi: 10.1523/JNEUROSCI.18-07-02720.1998.
The effects of pergolide, a mixed D1/D2 receptor agonist, and bromocriptine, a selective D2 receptor agonist, were assessed in a visual delay task to further investigate the "dopamine link" of working memory in humans and to look for differential D1 versus D2 receptor contributions. Two groups of 32 healthy young adults (16 female) received either 0.1 mg of pergolide or 2.5 mg of bromocriptine in a placebo-controlled cross-over design. A pretreatment with domperidone, a peripherally active D2 antagonist, was performed in both groups to reduce side effects. Interindividual differences in pharmacokinetics were controlled by the time course of serum prolactin inhibition. The working memory paradigm was a visuospatial delayed matching task; the location of a randomly generated seven-point pattern had to be memorized and compared after 2, 8, or 16 sec with a second pattern that was either identical or slightly shifted within a reference frame. The task was designed with the intention to present unique stimuli at each trial and to require minimal motor demands. Practice effects between the two pharmacological test days were minimized by training sessions that preceded the tests. The paradigm showed significant error and reaction time increases with longer delays. After comparable doses, only pergolide, but not bromocriptine, facilitated visuospatial working memory performance as demonstrated by a significant drug-by-delay interaction. These findings are in accordance with the monkey literature as well as with neuroanatomical findings, and they confirm a preferential role of prefrontal D1 receptors for working memory modulation in humans.
在一项视觉延迟任务中，评估了混合性D1/D2受体激动剂培高利特和选择性D2受体激动剂溴隐亭的作用，以进一步研究人类工作记忆的“多巴胺联系”，并探寻D1与D2受体的不同作用。两组各32名健康年轻成年人（16名女性）采用安慰剂对照交叉设计，分别服用0.1毫克培高利特或2.5毫克溴隐亭。两组均预先使用外周活性D2拮抗剂多潘立酮以减少副作用。通过血清催乳素抑制的时间进程来控制个体间的药代动力学差异。工作记忆范式为视觉空间延迟匹配任务；必须记住随机生成的七点图案的位置，并在2秒、8秒或16秒后与在参考框架内相同或略有偏移的第二个图案进行比较。该任务的设计目的是在每次试验中呈现独特的刺激，并将运动需求降至最低。通过在测试前进行训练，将两个药理测试日之间的练习效应降至最低。该范式显示，随着延迟时间延长，错误率和反应时间显著增加。在服用相当剂量后，只有培高利特而非溴隐亭促进了视觉空间工作记忆表现，这表现为显著的药物与延迟时间的交互作用。这些发现与猴子研究文献以及神经解剖学发现一致，证实了前额叶D1受体在人类工作记忆调节中具有优先作用。
