Amnesia produced by altered release of neurotransmitters after intraamygdala injections of a protein synthesis inhibitor
Amnesia produced by altered release of neurotransmitters after intraamygdala injections of a protein synthesis inhibitor
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DOI：
10.1073/pnas.0705195104
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发表时间：
2007-07-24
影响因子：
11.1
通讯作者：
Gold, Paul E.
中科院分区：
文献类型：
--
作者：
Canal, Clinton E.;Chang, Qing;Gold, Paul E.
由蛋白质合成抑制剂（如大霉素）引起的健忘症为长期记忆的形成需要从头合成蛋白质这一流行观点提供了主要支持。然而，抑制蛋白质合成可能会破坏其他神经功能，从而干扰记忆的形成。抑制回避训练前的杏仁核内注射大霉素48小时后测试的大鼠记忆受损。去甲肾上腺素（NE）、多巴胺（DA）和血清素的释放，在注射异霉素的部位测量，迅速增加了大约1000 - 17000%，远远高于正常情况下的水平。NE和DA的释放随后在48小时恢复前的几个小时内远远低于基线。杏仁核内注射β -肾上腺素能受体拮抗剂或激动剂，每次都可以减弱大霉素后NE释放的增加和减少的影响，减轻大霉素诱导的健忆症。此外，与大霉素对记忆的影响类似，训练前在杏仁核内注射高剂量的NE会在训练后48小时测试记忆受损。这些发现表明，神经递质释放的改变可能介导了由大霉素引起的健忘症，并进一步提出了关于记忆形成的许多分子理论的经验基础的重要问题。
Amnesia produced by protein synthesis inhibitors such as anisomycin provides major support for the prevalent view that the formation of long-lasting memories requires de novo protein synthesis. However, inhibition of protein synthesis might disrupt other neural functions to interfere with memory formation. Intraamygdala injections of anisomycin before inhibitory avoidance training impaired memory in rats tested 48 h later. Release of norepinephrine (NE), dopamine (DA), and serotonin, measured at the site of anisomycin infusions, increased quickly by approximate to 1,000-17,000%, far above the levels seen under normal conditions. NE and DA release later decreased far below baseline for several hours before recovering at 48 h. Intraamygdala injections of a beta-adrenergic receptor antagonist or agonist, each timed to blunt effects of increases and decreases in NE release after anisomycin, attenuated anisomycin-induced amnesia. In addition, similar to the effects on memory seen with anisomycin, intraamygdala injections of a high dose of NE before training impaired memory tested at 48 h after training. These findings suggest that altered release of neuro-transmitters may mediate amnesia produced by anisomycin and, further, raise important questions about the empirical bases for many molecular theories of memory formation.