Canal Clinton E, Chang Qing, Gold Paul E
Neuroscience Program, Department of Animal Sciences, University of Illinois at Urbana-Champaign, Champaign, IL 61820, USA.
Proc Natl Acad Sci U S A. 2007 Jul 24;104(30):12500-5. doi: 10.1073/pnas.0705195104. Epub 2007 Jul 18.
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 approximately 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 neurotransmitters may mediate amnesia produced by anisomycin and, further, raise important questions about the empirical bases for many molecular theories of memory formation.
诸如茴香霉素等蛋白质合成抑制剂所导致的失忆，为持久记忆的形成需要从头合成蛋白质这一普遍观点提供了主要支持。然而，蛋白质合成的抑制可能会扰乱其他神经功能，从而干扰记忆形成。在抑制性回避训练前向杏仁核内注射茴香霉素，会损害48小时后接受测试的大鼠的记忆。在茴香霉素注入部位测量到的去甲肾上腺素（NE）、多巴胺（DA）和5-羟色胺的释放迅速增加了约1000%-17000%，远高于正常情况下的水平。NE和DA的释放在数小时内随后降至基线以下，然后在48小时时恢复。向杏仁核内注射β-肾上腺素能受体拮抗剂或激动剂，每种药物的注射时间均能抑制茴香霉素后NE释放的增加和减少的影响，从而减轻了茴香霉素诱导的失忆。此外，与茴香霉素对记忆的影响类似，在训练前向杏仁核内注射高剂量的NE会损害训练后48小时测试的记忆。这些发现表明，神经递质释放的改变可能介导了茴香霉素所致的失忆，并且进一步对许多记忆形成分子理论的实验基础提出了重要问题。
