Effects of chronic sazetidine-A, a selective α4β2 neuronal nicotinic acetylcholine receptors desensitizing agent on pharmacologically-induced impaired attention in rats.
Effects of chronic sazetidine-A, a selective α4β2 neuronal nicotinic acetylcholine receptors desensitizing agent on pharmacologically-induced impaired attention in rats.
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慢性sazetidine-A，一种选择性α4β2 神经元烟碱乙酰胆碱受体脱敏剂对药理学诱导的大鼠注意力受损的影响。
DOI：
10.1007/s00213-012-2895-6
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发表时间：
2013
影响因子：
3.4
通讯作者：
Levin,EdwardD
中科院分区：
文献类型：
--
作者：
Rezvani,AmirH;Cauley,Marty;Xiao,Yingxian;Kellar,KennethJ;Levin,EdwardD
尼古丁和烟碱激动剂已被证明可以改善注意力功能。烟碱受体很容易脱敏，所有烟碱激动剂也是脱敏剂。虽然受体激活和脱敏都是介导烟碱激动剂整体效应的机制的组成部分，但尚不清楚这两种相反的作用中的每一种如何有助于注意力的改善。氮杂环丁烷-A对α4β2烟碱受体具有高结合亲和力，并导致相对短暂的激活，随后是受体的长期脱敏。急性给药sazetidine-A已被证明可以显着提高注意力，扭转损伤所造成的毒蕈碱胆碱能拮抗剂东莨菪碱和NMDA谷氨酸拮抗剂dizocilpine.MethodsIn目前的研究中，我们测试了sazetidine-A（0，2，或6毫克/公斤/天）在Sprague-Dawley大鼠注意力的影响，慢性皮下输注。此外，我们调查了慢性sazetidine-A治疗引起的注意力障碍急性给药的0.02毫克/公斤东莨菪碱。ResultsDuring的第一周期间，6毫克/公斤/天sazetidine-A剂量显着逆转东莨菪碱引起的注意力障碍。在第3周和第4周期间，不再观察到东莨菪碱诱导的损伤，但沙泽替丁-A（6 mg/kg/天）自身显著改善了注意力表现。慢性sazetidine-A也减少了响应潜伏期和响应omittings.ConclusionsThis研究表明，类似于其急性影响，慢性输注sazetidine-A提高注意力的表现。结果提示，α4β2烟碱受体的脱敏和部分受体的激活可能在沙泽替丁-A改善注意效应中起重要作用。
RationaleNicotine and nicotinic agonists have been shown to improve attentional function. Nicotinic receptors are easily desensitized, and all nicotinic agonists are also desensitizing agents. Although both receptor activation and desensitization are components of the mechanism that mediates the overall effects of nicotinic agonists, it is not clear how each of the two opposed actions contributes to attentional improvements. Sazetidine-A has high binding affinity at α4β2 nicotinic receptors and causes a relatively brief activation followed by a long-lasting desensitization of the receptors. Acute administration of sazetidine-A has been shown to significantly improve attention by reversing impairments caused by the muscarinic cholinergic antagonist scopolamine and the NMDA glutamate antagonist dizocilpine.MethodsIn the current study, we tested the effects of chronic subcutaneous infusion of sazetidine-A (0, 2, or 6 mg/kg/day) on attention in Sprague-Dawley rats. Furthermore, we investigated the effects of chronic sazetidine-A treatment on attentional impairment induced by an acute administration of 0.02 mg/kg scopolamine.ResultsDuring the first week period, the 6-mg/kg/day sazetidine-A dose significantly reversed the attentional impairment induced by scopolamine. During weeks 3 and 4, the scopolamine-induced impairment was no longer seen, but sazetidine-A (6 mg/kg/day) significantly improved attentional performance on its own. Chronic sazetidine-A also reduced response latency and response omissions.ConclusionsThis study demonstrated that similar to its acute effects, chronic infusions of sazetidine-A improve attentional performance. The results indicate that the desensitization of α4β2 nicotinic receptors with some activation of these receptors may play an important role in improving effects of sazetidine-A on attention.
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