Levin E D, McGurk S R, Rose J E, Butcher L L
Nicotine Research Lab, VA Medical Center, Durham, NC 27705.
Pharmacol Biochem Behav. 1989 Aug;33(4):919-22. doi: 10.1016/0091-3057(89)90494-2.
Pharmacological blockade of either nicotinic or muscarinic cholinergic receptors has been found to impair choice accuracy in the radial-arm maze. Simultaneous blockade of both of these receptor types causes an additive impairment. However, despite these common effects, nicotinic and muscarinic receptors have been found to have differential involvement with dopamine receptors. The cognitive impairment caused by the muscarinic antagonist scopolamine is reversed by the D1 antagonist SCH 23390 but is unaffected by the D2 antagonist raclopride. In contrast, the cognitive impairment caused by the nicotinic antagonist mecamylamine is unaffected by SCH 23390 but is potentiated by raclopride. In the current study, the D2 agonist LY 171555 was found to be effective in reversing the radial-arm maze choice accuracy impairment caused by mecamylamine. In contrast, the D1 agonist SKF 38393 was not found to be effective. Thus, we have found selective dopaminergic D1 and D2 treatments which counteract the adverse cognitive effects of either nicotinic or muscarinic blockade. A combination of these treatments may be useful in treating the cognitive effects of generalized cholinergic underactivation.
已发现对烟碱型或毒蕈碱型胆碱能受体的药理学阻断会损害放射状臂迷宫中的选择准确性。同时阻断这两种受体类型会导致累加性损害。然而，尽管有这些共同作用，但已发现烟碱型和毒蕈碱型受体与多巴胺受体的参与情况有所不同。毒蕈碱拮抗剂东莨菪碱引起的认知障碍可被D1拮抗剂SCH 23390逆转，但不受D2拮抗剂雷氯必利的影响。相反，烟碱拮抗剂美加明引起的认知障碍不受SCH 23390的影响，但会被雷氯必利增强。在当前研究中，发现D2激动剂LY 171555可有效逆转美加明引起的放射状臂迷宫选择准确性损害。相反，未发现D1激动剂SKF 38393有效。因此，我们发现了选择性多巴胺能D1和D2治疗方法，可抵消烟碱型或毒蕈碱型阻断的不良认知作用。这些治疗方法的组合可能有助于治疗全身性胆碱能活性不足的认知影响。
