Levin E D, McGurk S R, Rose J E, Butcher L L
Department of Psychiatry, Duke University, Durham, North Carolina 27706.
Behav Neural Biol. 1990 Nov;54(3):271-99. doi: 10.1016/0163-1047(90)90639-n.
Both acetylcholinergic (ACh) and dopaminergic (DA) systems have been found to be crucial for the maintenance of accurate cognitive performance. In a series of studies examining those aspects of cognitive function revealed by the radial-arm maze, we have found that these two neurotransmitter systems interact in a complex fashion. Choice accuracy deficits in the radial-arm maze can be induced by blockade of either muscarinic- or nicotinic-ACh receptors. The choice accuracy deficit induced by blockade of muscarinic receptors with scopolamine can be reversed by the DA receptor blocker, haloperidol. The specific DA D1 blocker SCH 23390 also has this effect, whereas the specific D2 blocker raclopride does not, implying that it is D1 blockade that is critical for reversing the scopolamine effect. On the other hand, the choice accuracy deficit induced by nicotinic blockade with mecamylamine is potentiated by haloperidol. This effect is also seen with the D2 antagonist raclopride, but not with the D1 antagonist SCH 23390, implying that it is the D2 receptor which is important for the potentiation of the mecamylamine effect. The relevance of the D2 receptor for nicotinic actions on cognitive function is emphasized by the finding that the selective D2 agonist LY 171555 reverses the choice accuracy deficit caused by mecamylamine. Nicotinic and muscarinic blockade are synergistic in the deficit they produce. Antagonist doses subthreshold when given alone produce a pronounced impairment when given together. This latter deficit can be reversed by the D2 agonist LY 171555. These studies have outlined the complex nature of ACh-DA interactions with regard to cognitive function. Possible neural circuits for these interactions are discussed. The effectiveness of these selective DA treatments in reversing cognitive deficits due to ACh underactivation suggests a novel approach to treating cognitive dysfunction in syndromes such as Alzheimer's disease.
已发现乙酰胆碱能（ACh）和多巴胺能（DA）系统对于维持准确的认知表现至关重要。在一系列研究中，我们通过放射状臂迷宫研究认知功能的这些方面，发现这两种神经递质系统以复杂的方式相互作用。放射状臂迷宫中的选择准确性缺陷可由毒蕈碱型或烟碱型ACh受体的阻断诱导。用东莨菪碱阻断毒蕈碱受体所诱导的选择准确性缺陷可被DA受体阻断剂氟哌啶醇逆转。特异性DA D1阻断剂SCH 23390也有此作用，而特异性D2阻断剂雷氯必利则没有，这意味着是D1阻断对于逆转东莨菪碱效应至关重要。另一方面，用美加明进行烟碱阻断所诱导的选择准确性缺陷会被氟哌啶醇增强。D2拮抗剂雷氯必利也可见此效应，但D1拮抗剂SCH 23390则没有，这意味着对于增强美加明效应而言，D2受体很重要。选择性D2激动剂LY 171555可逆转美加明引起的选择准确性缺陷，这一发现强调了D2受体对于烟碱对认知功能作用的相关性。烟碱和毒蕈碱阻断在它们所产生的缺陷方面具有协同作用。单独给药时阈下剂量的拮抗剂合用时会产生明显的损害。后一种缺陷可被D2激动剂LY 171555逆转。这些研究概述了ACh - DA在认知功能方面相互作用的复杂性质。讨论了这些相互作用可能的神经回路。这些选择性DA治疗在逆转因ACh活性不足所致认知缺陷方面的有效性提示了一种治疗诸如阿尔茨海默病等综合征中认知功能障碍的新方法。
