WORKING-MEMORY PERFORMANCE AND CHOLINERGIC EFFECTS IN THE VENTRAL TEGMENTAL AREA AND SUBSTANTIA-NIGRA
WORKING-MEMORY PERFORMANCE AND CHOLINERGIC EFFECTS IN THE VENTRAL TEGMENTAL AREA AND SUBSTANTIA-NIGRA
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DOI：
10.1016/0006-8993(94)90964-4
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发表时间：
1994-09-19
期刊：
影响因子：
2.9
通讯作者：
AUMAN, JT
中科院分区：
文献类型：
--
作者：
LEVIN, ED;BRIGGS, SJ;AUMAN, JT
已经发现烟碱拮抗剂美加明在皮下注射后损害径向臂迷宫（RAM）中的工作记忆表现。或i. c. v.给药。美加明与多巴胺能（DA）系统有重要的相互作用。D-2拮抗剂雷氯必利可增强Mecamylamine诱导的RAM记忆缺陷，D-2激动剂喹吡罗可逆转Mecamylamine诱导的RAM记忆缺陷。已经发现烟碱激动剂烟碱在s.c.或i. c. v.给药。尼古丁诱导的RAM记忆改善通过D-2激动剂喹吡罗增强。中脑DA核、黑质（SN）和腹侧被盖区（VTA）具有相对密集的烟碱受体浓度，这可能是美加明和尼古丁的关键作用部位。在当前的研究中，在成年雌性Sprague-Dawley大鼠中检查了将美加明（1、3.3和10 μ g/侧）输注到SN（n = 12）和VTA（n = 13）中对辐射臂迷宫中工作记忆的影响。当注入SN或VTA时，10 μ g/侧剂量的美加明显著损害放射臂迷宫工作记忆表现。未观察到美加明对反应潜伏期的显著影响。烟碱激动剂野靛碱（0.1、0.33和1.0 μ g/侧）和尼古丁（0.3、1.0和3.3 μ g/侧）以平衡顺序给药。高剂量金雀花碱（1 μ g/侧）几乎导致选择准确性的显著缺陷。尼古丁轻微降低了选择的准确性，但在这项研究中并不显着。然后研究了尼古丁和美加明的相互作用。剂量为1.0微克/侧的尼古丁引起的选择准确性显着下降。有趣的是，3.3 μ g/侧剂量的美加明显著逆转了这一点。毒蕈碱拮抗剂东莨菪碱（1，3.3和10 μ g/侧）和毒蕈碱激动剂毛果芸香碱（3，10和30 μ g/侧）的研究没有检测到RAM选择准确性的显着影响。这些数据支持中脑DA核的尼古丁神经支配参与记忆功能。
The nicotinic antagonist mecamylamine has been found to impair working memory performance in the radial-arm maze (RAM) after s.c. or i.c.v. administration. Mecamylamine has important interactions with dopaminergic (DA) systems. Mecamylamine-induced memory deficits in the RAM are potentiated by the D-2 antagonist raclopride and reversed by the D-2 agonist quinpirole. The nicotinic agonist nicotine has been found to improve working memory performance in the RAM after s.c. or i.c.v. administration. Nicotine-induced memory improvement in the RAM is potentiated by the D-2 agonist quinpirole. The midbrain DA nuclei, the substantia nigra (SN) and the ventral tegmental area (VTA) have relatively dense concentrations of nicotinic receptors which may be critical sites of action for mecamylamine and nicotine. In the current study, the effects of mecamylamine (1, 3.3 and 10 mu g/side) infusions into the SN (n = 12) and VTA (n = 13) on working memory in the radial-arm maze were examined in adult female Sprague-Dawley rats. The 10-mu g/side dose of mecamylamine significantly impaired radial-arm maze working memory performance when infused into either the SN or VTA. No significant effects of mecamylamine on response latency were seen. The nicotinic agonists cytisine (0.1, 0.33 and 1.0 mu g/side) and nicotine (0.3, 1.0 and 3.3 mu g/side) were administered in a counterbalanced order. The high dose of cytisine (1 mu g/side) nearly caused a significant deficit in choice accuracy. Nicotine slightly depressed choice accuracy but not significantly in this study. The interaction of nicotine and mecamylamine was then studied. A dose of 1.0 mu g/side of nicotine caused a significant decrease in choice accuracy. Interestingly, this was significantly reversed by a 3.3-mu g/side dose of mecamylamine. Studies of the muscarinic antagonist scopolamine (1, 3.3 and 10 mu g/side) and the muscarinic agonist pilocarpine (3, 10 and 30 mu g/side) did not detect significant effects on RAM choice accuracy. These data support the involvement of nicotinic innervation of the midbrain DA nuclei in memory function.