Ventral hippocampal α4β2 nicotinic receptors and chronic nicotine effects on memory
Ventral hippocampal α4β2 nicotinic receptors and chronic nicotine effects on memory
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DOI：
10.1016/s0028-3908(00)00099-x
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发表时间：
2000-01-01
影响因子：
4.7
通讯作者：
Levin, ED
中科院分区：
文献类型：
--
作者：
Bancroft, A;Levin, ED
长期给药尼古丁已多次被证明可以促进大鼠在放射状臂迷宫中的工作记忆功能。这种影响的关键神经机制仍在研究中。慢性尼古丁诱导的记忆改善的尼古丁性质被发现被慢性美甲胺共输注阻断。海马体似乎也至关重要。海马伊博滕酸损伤阻断了这种作用。在海马体中，我们发现α 4 β 2烟碱受体亚型参与记忆功能。急性海马腹侧输注α 4 β 2烟碱拮抗剂二氢β -红血碱（DH β ae）显著降低桡臂迷宫的工作记忆表现。当前研究的目的是确定腹侧海马体中alpha4 β 2受体对慢性尼古丁治疗的记忆增强作用的重要性。成年雌性Sprague-Dawley大鼠在8臂放射状迷宫中训练，并在双侧海马腹侧插管。在接受尼古丁治疗的大鼠体内也植入了每天每公斤5毫克的慢性尼古丁渗透微型泵。对照大鼠接受纯盐水微型泵。术后4周内，每只大鼠双侧海马分别注射0、2、6和18杯DH β ae，并测试其在桡臂迷宫中的记忆表现。急性海马DH β输注对桡臂迷宫选择准确性有剂量相关影响。这种急性海马DH β诱导的选择准确性损伤可通过慢性全身尼古丁输注消除。慢性尼古丁联合急性载体海马输注未见改变选择的准确性。在没有慢性尼古丁给药的情况下，急性海马DH β ae没有改变反应潜伏期，但它确实减弱了慢性尼古丁输注引起的反应潜伏期降低。当不给慢性尼古丁时，湿狗奶昔不受海马DH β的影响。慢性尼古丁输注显著增加了湿狗的摇晃。海马内DH β显著增强了这一作用。目前的研究结果强化了腹侧海马α - 4 β - 2烟碱受体对记忆功能很重要的假设。这些受体也可能在与慢性尼古丁治疗相关的其他方面的行为发展中发挥作用。(C) 2000, Elsevier Science Ltd.出版
Chronic nicotine administration has been repeatedly shown to facilitate working memory function in rats on the radial-arm maze. The critical neural mechanisms for this effect are still being discovered. The nicotinic nature of the chronic nicotine induced memory improvement is supported by the finding that it is blocked by chronic mecamylamine co-infusion. The hippocampus also appears to be critically important. Hippocampal ibotenic acid lesions block the effect. Within the hippocampus, we have found that the alpha4 beta2 nicotinic receptor subtype is involved in memory functioning. Acute ventral hippocampal infusions of the alpha4 beta2 nicotinic antagonist dihydro-beta -erythroidine (DH betaE) significantly decreased working memory performance in the radial-arm maze. The aim of the current study was to determine the importance of alpha4 beta2 receptors within the ventral hippocampus for the memory enhancing effects of chronic nicotine treatment. Adult female Sprague-Dawley rats were trained on the 8-arm radial maze and were cannulated bilaterally in the ventral hippocampus. Osmotic minipumps administering chronic nicotine at a rate of 5 mg per kg per day were also implanted in the nicotine treatment rats. Control rats received saline-only minipumps. For a period of 4 weeks after surgery, each rat received bilateral hippocampal infusions of 0, 2, 6 and 18 mug per side of DH betaE and tested for memory performance on the radial-arm maze. Radial-arm maze choice accuracy was impaired by acute hippocampal DH betaE infusion in a dose-related fashion. This acute hippocampal DH betaE-induced choice accuracy impairment was eliminated by chronic systemic nicotine infusion. Chronic nicotine in combination with acute vehicle hippocampal infusion was not seen to alter choice accuracy. Response latency was not found to be altered by acute hippocampal DH betaE in the absence of chronic nicotine administration, but it did attenuate the response latency reduction induced by chronic nicotine infusion. Wet dog shakes were not found to be affected by hippocampal DH betaE when given without chronic nicotine. Wet dog shakes were significantly increased by chronic nicotine infusion. Intra-hippocampal DH betaE significantly potentiated this effect. The results from the current study reinforce the hypothesis that ventral hippocampal alpha4 beta2 nicotinic receptors are important for memory function. These receptors may also have a role to play in the development of other aspects of behavior associated with chronic nicotine treatment. (C) 2000 Published by Elsevier Science Ltd.