Levin E D
Department of Psychology, University of California, Los Angeles 90024.
Behav Neural Biol. 1988 Sep;50(2):240-5. doi: 10.1016/s0163-1047(88)90911-9.
Recent evidence indicates that acetylcholine and dopamine play complementary roles in cognitive as well as motor functions. In our previous study, the dopamine receptor blocker, haloperidol, was found to attenuate the radial-arm maze choice accuracy deficit caused by the muscarinic acetylcholine receptor blocker, scopolamine. Haloperidol has activity in blocking both D1 and D2 dopamine receptor subtypes. The current study was conducted to determine whether this dopamine-acetylcholine interaction specifically involved D1 or D2 dopamine receptors. The D1 antagonist, SCH 23390, and the D2 antagonist, raclopride, were administered with a dose of scopolamine which caused choice accuracy deficits in the radial-arm maze. The scopolamine-induced deficit was reversed by SCH 23390, the D1 antagonist, indicating that D1 blockade alone is sufficient to reverse the amnestic effects of muscarinic blockade. There was no indication in this study that the D2 blocker, raclopride, had a similar effect. However, this does not mean that such an effect may not be present at other doses of raclopride or with other D2 antagonists. The present finding that D1 blockade counteracts scopolamine-induced cognitive dysfunction not only furthers the understanding of dopamine-acetylcholine relationships in cognitive function, it also suggests a promising direction for the development of treatments for cognitive dysfunction due to cholinergic loss.
最近的证据表明，乙酰胆碱和多巴胺在认知及运动功能中发挥着互补作用。在我们之前的研究中，发现多巴胺受体阻滞剂氟哌啶醇可减轻毒蕈碱型乙酰胆碱受体阻滞剂东莨菪碱所导致的放射状臂迷宫选择准确性缺陷。氟哌啶醇具有阻断D1和D2两种多巴胺受体亚型的活性。本研究旨在确定这种多巴胺 - 乙酰胆碱相互作用是否特别涉及D1或D2多巴胺受体。将D1拮抗剂SCH 23390和D2拮抗剂雷氯必利与一定剂量的东莨菪碱一起给药，该剂量的东莨菪碱会导致放射状臂迷宫中的选择准确性缺陷。D1拮抗剂SCH 23390逆转了东莨菪碱诱导的缺陷，表明仅阻断D1就足以逆转毒蕈碱阻断的遗忘效应。本研究未表明D2阻滞剂雷氯必利有类似作用。然而，这并不意味着在雷氯必利的其他剂量或与其他D2拮抗剂一起使用时可能不存在这种作用。目前发现阻断D1可抵消东莨菪碱诱导的认知功能障碍，这不仅进一步加深了对认知功能中多巴胺 - 乙酰胆碱关系的理解，还为因胆碱能丧失导致的认知功能障碍的治疗开发指明了一个有前景的方向。
