Levin E D, Rose J E
Nicotine Research Laboratory, VA Medical Center, Durham, NC 27705.
Pharmacol Biochem Behav. 1991 Feb;38(2):243-6. doi: 10.1016/0091-3057(91)90272-4.
Pharmacological blockade of muscarinic cholinergic (ACh) receptors has been found to impair choice accuracy in a variety of tasks including the radial-arm maze. The cognitive impairment caused by the muscarinic antagonist scopolamine is reversed by the dopaminergic (DA) antagonist haloperidol as well as the selective D1 antagonist SCH 23390. In the current study, interactions were studied between scopolamine and selective agonists of D1 (SCH 38393) and D2 (quinpirole) receptors. Surprisingly, the D1 agonist SKF 38393 was found to significantly alleviate the scopolamine-induced choice accuracy deficit. In contrast, the D2 agonist quinpirole was not found to significantly alter the effects of scopolamine on choice accuracy but did have supra-additive effects of increasing choice latency. Both the D1 agonist SKF 38393 and the D1 antagonist SCH 23390 have been found to reverse the choice accuracy deficit caused by scopolamine and the deficit resulting from lesions of the medial projection from the basal forebrain to the cortex. Possible mechanisms for these effects are discussed.
已发现，在包括放射状臂迷宫在内的各种任务中，对毒蕈碱型胆碱能（ACh）受体进行药理学阻断会损害选择准确性。毒蕈碱拮抗剂东莨菪碱引起的认知障碍可被多巴胺能（DA）拮抗剂氟哌啶醇以及选择性D1拮抗剂SCH 23390逆转。在本研究中，研究了东莨菪碱与D1（SCH 38393）和D2（喹吡罗）受体的选择性激动剂之间的相互作用。令人惊讶的是，发现D1激动剂SKF 38393可显著减轻东莨菪碱诱导的选择准确性缺陷。相比之下，未发现D2激动剂喹吡罗能显著改变东莨菪碱对选择准确性的影响，但确实具有增加选择潜伏期的超相加效应。已发现D1激动剂SKF 38393和D1拮抗剂SCH 23390均可逆转由东莨菪碱引起的选择准确性缺陷以及由基底前脑到皮质的内侧投射损伤导致的缺陷。讨论了这些效应的可能机制。
