Second-by-second analysis of alpha 7 nicotine receptor regulation of glutamate release in the prefrontal cortex of awake rats.
Second-by-second analysis of alpha 7 nicotine receptor regulation of glutamate release in the prefrontal cortex of awake rats.
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DOI：
10.1002/syn.20693
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发表时间：
2009-12
期刊：
影响因子：
2.3
通讯作者：
Bruno, John P.
中科院分区：
文献类型：
--
作者：
Konradsson-Geuken, Asa;Gash, Clelland R.;Alexander, Kathleen;Pomerleau, Francois;Huettl, Peter;Gerhardt, Greg A.;Bruno, John P.
这些实验利用了一种基于酶的微电极，选择性地逐秒检测细胞外谷氨酸，以揭示自由运动大鼠前额叶皮层（PFC）中谷氨酸释放的α 7烟碱调节。大鼠接受皮质内输注非选择性烟碱激动剂尼古丁（1.0 μ g/0.4 μ L）或选择性α 7激动剂胆碱（2.0 mM/0.4 μ L）。在用α 7拮抗剂α-银环蛇毒素（α-BGT，10 μ M）或犬尿氨酸（10 μ M）（星形胶质细胞衍生的负变构α 7调节剂犬尿烯酸的前体）预处理的动物亚组中评估了药物诱导的谷氨酸释放的选择性。尼古丁局部给药增加谷氨酸信号（最大振幅= 4.3 ± 0.6 μ M），在493 ± 80秒内清除至基线水平。用α-BGT或犬尿氨酸预处理分别使尼古丁诱导的谷氨酸减少61%和60%。局部给予胆碱也增加谷氨酸信号（最大幅度= 6.3 ± 0.9 μ M）。与尼古丁诱发的谷氨酸释放相反，胆碱诱发的信号被更快地清除（28 ± 6秒），并且用α-BGT或犬尿氨酸预处理完全阻断刺激的谷氨酸释放。使用揭示体内谷氨酸释放和清除的时间动力学的方法，这些数据表明α 7和非α 7介导的皮质谷氨酸释放的烟碱调节。此外，这些数据还可能提供了最近关注α 7完全和部分激动剂作为治疗药物治疗精神分裂症中皮质介导的认知缺陷的机制。
These experiments utilized an enzyme-based microelectrode selective for the second-by-second detection of extracellular glutamate to reveal the α7-based nicotinic modulation of glutamate release in the prefrontal cortex (PFC) of freely moving rats. Rats received intra-cortical infusions of the non-selective nicotinic agonist nicotine (1.0 μg/0.4 μL) or the selective α7 agonist choline (2.0 mM/0.4 μL). The selectivity of drug-induced glutamate release was assessed in subgroups of animals pre-treated with the α7 antagonist, α-bungarotoxin (α-BGT, 10 μM) or kynurenine (10 μM) the precursor of the astrocyte-derived, negative allosteric α7 modulator kynurenic acid. Local administration of nicotine increased glutamate signals (maximum amplitude = 4.3 ± 0.6 μM) that were cleared to baseline levels in 493 ± 80 sec. Pre-treatment with α-BGT or kynurenine attenuated nicotine-induced glutamate by 61% and 60%, respectively. Local administration of choline also increased glutamate signals (maximum amplitude = 6.3 ± 0.9 μM). In contrast to nicotine-evoked glutamate release, choline-evoked signals were cleared more quickly (28 ± 6 sec) and pre-treatment with α-BGT or kynurenine completely blocked the stimulated glutamate release. Using a method that reveals the temporal dynamics of in vivo glutamate release and clearance, these data indicate a nicotinic modulation of cortical glutamate release that is both α7 – and non-α7-mediated. Furthermore, these data may also provide a mechanism underlying the recent focus on α7 full and partial agonists as therapeutic agents in the treatment of cortically-mediated cognitive deficits in schizophrenia.
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影响因子：
5.3
作者：
Bitner, Robert S.;Bunnelle, William H.;Gopalakrishnan, Murali
通讯作者：
Gopalakrishnan, Murali
影响因子：
3.4
作者：
Foulds, J;Stapleton, J;Russell, MAH
通讯作者：
Russell, MAH
影响因子：
2.9
作者：
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通讯作者：
Chiba, T
影响因子：
7.4
作者：
Kulagina, NV;Shankar, L;Michael, AC
通讯作者：
Michael, AC
影响因子：
64.8
作者：
Gray, R;Rajan, AS;Dani, JA
通讯作者：
Dani, JA