Rämä P, Linnankoski I, Tanila H, Pertovaara A, Carlson S
Department of Physiology, University of Helsinki, Finland.
Pharmacol Biochem Behav. 1996 Nov;55(3):415-22. doi: 10.1016/s0091-3057(96)00111-6.
The effects of a highly selective alpha-2 adrenergic agonist medetomidine and its antagonist atipamezole were studied on the delayed response task performance of aged monkeys. Medetomidine, at the dose of 1.0 micrograms/kg, improved the memory task performance, whereas atipamezole had no effect on the performance at any dose. It has earlier been shown that alpha-2 adrenergic agonists clonidine and guanfacine improve age-associated memory impairment, but also contradictory effects of clonidine have been reported. There is evidence that the ability of alpha-2 agonists to improve DR task performance is due to its selective action on the alpha-2A receptor subtype. Clonidine and medetomidine are much less selective than guanfacine with respect to alpha-2A and alpha-2B receptor subtypes. Therefore, we also studied the effect of guanfacine on the memory task performance of the same aged monkeys in the same testing conditions to compare the effectiveness of these two alpha-2 adrenergic compounds. Guanfacine improved memory task performance at the dose of 0.0001 mg/kg. The results indicate that alpha-2 agonists, independent of their different selectivity with respect to alpha-2A/2B receptor subtypes, are beneficial drugs in improving the performance in the delayed response task.
研究了高选择性α-2肾上腺素能激动剂美托咪定及其拮抗剂阿替美唑对老年猴子延迟反应任务表现的影响。剂量为1.0微克/千克的美托咪定改善了记忆任务表现，而阿替美唑在任何剂量下对表现均无影响。此前已有研究表明，α-2肾上腺素能激动剂可乐定和胍法辛可改善与年龄相关的记忆障碍，但也有关于可乐定矛盾作用的报道。有证据表明，α-2激动剂改善延迟反应任务表现的能力归因于其对α-2A受体亚型的选择性作用。就α-2A和α-2B受体亚型而言，可乐定和美托咪定的选择性远低于胍法辛。因此，我们还在相同测试条件下研究了胍法辛对同组老年猴子记忆任务表现的影响，以比较这两种α-2肾上腺素能化合物的有效性。剂量为0.0001毫克/千克的胍法辛改善了记忆任务表现。结果表明，α-2激动剂，无论其对α-2A/2B受体亚型的选择性如何，都是改善延迟反应任务表现的有益药物。
