Nicotine ameliorates NMDA receptor antagonist-induced deficits in contextual fear conditioning through high-affinity nicotinic acetylcholine receptors in the hippocampus.
Nicotine ameliorates NMDA receptor antagonist-induced deficits in contextual fear conditioning through high-affinity nicotinic acetylcholine receptors in the hippocampus.
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DOI：
10.1016/j.neuropharm.2010.12.004
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发表时间：
2011-03
影响因子：
4.7
通讯作者：
Gould, Thomas J.
中科院分区：
文献类型：
--
作者：
Andre, Jessica M.;Leach, Prescott T.;Gould, Thomas J.
NMDA -谷氨酸受体（NMDARs）和烟碱-乙酰胆碱受体（nAChRs）都参与学习和突触可塑性。越来越多的证据表明，这些受体介导的过程可能相互作用，以调节学习；然而，人们对参与这些相互作用过程的神经基质知之甚少。本研究研究了尼古丁对雄性C57BL/6J小鼠MK-801马来酸氢（MK-801）和dl -2-氨基-5-磷酸戊酸（APV）诱导的情境恐惧条件反射中断的影响，通过直接输注药物和选择性nAChR拮抗剂来确定所涉及的脑区和nAChR亚型。用MK-801治疗的小鼠显示出上下文恐惧条件反射的缺陷，尼古丁可以改善这种缺陷。直接药物输注表明，NMDAR拮抗剂破坏海马功能，尼古丁在海马背侧起作用，改善学习障碍。高亲和的nAChR拮抗剂二氢β-红血碱氢溴化（DhβE）阻断了尼古丁对mk -801诱导的缺陷的作用，而α7 nAChR拮抗剂柠檬酸盐水合甲基地碱（MLA）则没有。这些结果表明，NMDARs和nachr可能介导涉及情境恐惧条件反射的相似海马过程。此外，这些结果可能对开发与精神分裂症相关的认知缺陷的有效治疗方法有意义，因为大部分精神分裂症患者表现出与NMDAR功能障碍和吸烟相关的认知缺陷，其发生率远高于健康人群，这可能是改善认知缺陷的一种尝试。
NMDA glutamate receptors (NMDARs) and nicotinic acetylcholine receptors (nAChRs) are both involved in learning and synaptic plasticity. Increasing evidence suggests processes mediated by these receptors may interact to modulate learning; however, little is known about the neural substrates involved in these interactive processes. The present studies investigated the effects of nicotine on MK-801 hydrogen maleate (MK-801) and DL-2-Amino-5-phosphonovaleric acid (APV) induced disruption of contextual fear conditioning in male C57BL/6J mice, using direct drug infusion and selective nAChR antagonists to define the brain regions and the nAChR subtypes involved. Mice treated with MK-801 showed a deficit in contextual fear conditioning that was ameliorated by nicotine. Direct drug infusion demonstrated that the NMDAR antagonists disrupted hippocampal function and that nicotine acted in the dorsal hippocampus to ameliorate the deficit in learning. The high-affinity nAChR antagonist Dihydro-β-erythroidine hydrobromide (DhβE) blocked the effects of nicotine on MK-801-induced deficits while the α7 nAChR antagonist methyllycaconitine citrate salt hydrate (MLA) did not. These results suggest that NMDARs and nAChRs may mediate similar hippocampal processes involved in contextual fear conditioning. Furthermore, these results may have implications for developing effective therapeutics for the cognitive deficits associated with schizophrenia because a large subset of patients with schizophrenia exhibit cognitive deficits that may be related to NMDAR dysfunction and smoke at much higher rates than the healthy population, which may be an attempt to ameliorate cognitive deficits.
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影响因子：
3.4
作者：
Arthur, D;Levin, ED
通讯作者：
Levin, ED
DOI：
10.1016/0169-328x(94)00247-c
发表时间：
1995-04-01
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
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通讯作者：
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影响因子：
3.4
作者：
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通讯作者：
Gould, Thomas J.
影响因子：
7.6
作者：
Breese, CR;Lee, MJ;Leonard, S
通讯作者：
Leonard, S
影响因子：
3.5
作者：
Bast, T;Zhang, WN;Feldon, J
通讯作者：
Feldon, J