Dopamine D1 and D2 receptors differ with respect to patterns of regional brain distribution and behavioral effects. Pre-clinical work suggests that D1 agonists enhance working memory, but the absence of selective D1 agonists has constrained using this approach in humans. This study examines working memory performance in mild traumatic brain injury (mTBI) patients when given pergolide, a mixed D1/D2 agonist, compared with bromocriptine, a selective D2 agonist. Fifteen individuals were studied 1 month after mTBI and compared with 17 healthy controls. At separate visits, participants were administered 1.25 mg bromocriptine or 0.05 mg pergolide prior to functional magnetic resonance imaging (MRI) using a working memory task (visual-verbal n-back). Results indicated a significant group-by-drug interaction for mean performance across n-back task conditions, where the mTBI group showed better performance on pergolide relative to bromocriptine, whereas controls showed the opposite pattern. There was also a significant effect of diagnosis, where mTBI patients performed worse than controls, particularly while on bromocriptine, as shown in our prior work. Functional MRI activation during the most challenging task condition (3-back > 0-back contrast) showed a significant group-by-drug interaction, with the mTBI group showing increased activation relative to controls in working memory circuitry while on pergolide, including in the left inferior frontal gyrus. Across participants there was a positive correlation between change in activation in this region and change in performance between drug conditions. Results suggest that activation of the D1 receptor may improve working memory performance after mTBI. This has implications for the development of pharmacological strategies to treat cognitive deficits after mTBI.

中文翻译：

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培高利特和溴隐亭对轻度创伤性脑损伤后工作记忆表现和脑激活的不同影响。

多巴胺 D1 和 D2 受体在区域脑分布模式和行为影响方面有所不同。临床前研究表明 D1 激动剂增强了工作记忆，但选择性 D1 激动剂的缺乏限制了在人类中使用这种方法。本研究检查了轻度创伤性脑损伤 (mTBI) 患者在给予培高利特（一种混合 D1/D2 激动剂）与溴隐亭（一种选择性 D2 激动剂）相比时的工作记忆表现。在 mTBI 后 1 个月对 15 名个体进行了研究，并与 17 名健康对照者进行了比较。在单独的访问中，参与者在使用工作记忆任务（视觉-语言 n-back）进行功能性磁共振成像 (MRI) 之前给予 1.25 mg 溴隐亭或 0.05 mg 培高利特。结果表明，在 n-back 任务条件下的平均表现存在显着的组间相互作用，其中 mTBI 组相对于溴隐亭在培高利特上表现出更好的表现，而对照组表现出相反的模式。诊断也有显着影响，如我们之前的工作所示，mTBI 患者的表现比对照组差，特别是在使用溴隐亭时。在最具挑战性的任务条件下（3-back > 0-back contrast）的功能性 MRI 激活显示出显着的组间相互作用，mTBI 组在使用培高利特时显示出相对于工作记忆电路的控制增加的激活，包括在左侧额下回。在参与者中，该区域的激活变化与药物条件之间的性能变化之间存在正相关关系。结果表明，D1 受体的激活可能会改善 mTBI 后的工作记忆表现。这对开发治疗 mTBI 后认知缺陷的药理学策略具有重要意义。