POSTSYNAPTIC ALPHA-2 RECEPTOR STIMULATION IMPROVES MEMORY IN AGED MONKEYS - INDIRECT EFFECTS OF YOHIMBINE VERSUS DIRECT EFFECTS OF CLONIDINE
POSTSYNAPTIC ALPHA-2 RECEPTOR STIMULATION IMPROVES MEMORY IN AGED MONKEYS - INDIRECT EFFECTS OF YOHIMBINE VERSUS DIRECT EFFECTS OF CLONIDINE
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DOI：
10.1016/0197-4580(93)90044-c
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发表时间：
1993-11-01
影响因子：
4.2
通讯作者：
CAI, JX
中科院分区：
文献类型：
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作者：
ARNSTEN, AFT;CAI, JX
极低剂量(0.00001毫克/公斤)的α-2肾上腺素能拮抗剂育亨宾改善了一组老年猴子的工作记忆能力。改善似乎是由于去甲肾上腺素(NE)释放到突触后α-2肾上腺素受体的增加，因为这种反应被突触后的α-2拮抗剂SKF104078阻断。小剂量育亨宾治疗的认知增强作用可能依赖于老年动物保留完整的内源性NE系统。与育亨宾相反，α-2激动剂可乐定改善了空气老化动物的工作记忆。在本研究中，可乐定的有益作用也被突触后拮抗剂SKF104078和SKF104856阻断，这表明可乐定是通过直接刺激突触后α-2肾上腺素受体发挥作用的。将有益剂量的可乐定(0.01 mg/kg)和育亨宾(0.00001 mg/kg)联合使用，以确定它们是否会产生增强记忆的相加作用。这一策略在NE系统完整的年轻猴子身上是成功的，但在老年猴子身上无效。这些发现表明，在老年猴子中，通过增加NE释放间接刺激突触后α-2受体的药物不如直接作用于突触后α-2受体的替代NE的激动剂可靠。
Very low doses (0.00001 mg/kg) of the alpha-2 adrenergic antagonist, yohimbine, improved working memory performance in a subset of aged monkeys. Improvement appeared to result from increased norepinephrine (NE) release onto postsynaptic alpha-2 adrenoceptors, as the response was blocked by the ''postsynaptic'' alpha-2 antagonist, SKF104078. Cognitive-enhancing effects of low dose yohimbine treatment may depend on aged animals retaining an intact, endogenous NE system. In contrast to yohimbine, the alpha-2 agonist, clonidine, has improved working memory in air aged animals examined. In the present study, clonidine's beneficial effects were also blocked by the postsynaptic antagonists SKF104078 and SKF104856, suggesting that clonidine acts by directly stimulating postsynaptic alpha-2 adrenoceptors. Beneficial doses of clonidine (0.01 mg/kg) and yohimbine (0.00001 mg/kg) were combined to see if they would produce additive effects on memory enhancement. This strategy was successful in young monkeys with intact NE systems but was not effective in the aged monkeys. These findings demonstrate that drugs that indirectly stimulate postsynaptic alpha-2 receptors by increasing NE release are not as reliable in aged monkeys as directly acting agonists that can replace NE at postsynaptic alpha-2 receptors.