Neuroscience Program, College of Medicine, University of Illinois at Urbana-Champaign, Champaign, IL 61820, USA.
Neurobiol Learn Mem. 2011 Sep;96(2):136-42. doi: 10.1016/j.nlm.2011.03.007. Epub 2011 Mar 29.
When administered near the time of training, protein synthesis inhibitors such as anisomycin impair later memory. A common interpretation of these findings is that memory consolidation requires new protein synthesis initiated by training. However, recent findings support an alternative interpretation that abnormally large increases in neurotransmitter release after injections of anisomycin may be responsible for producing amnesia. In the present study, a local anesthetic was administered prior to anisomycin injections in an attempt to mitigate neurotransmitter actions and thereby attenuate the resulting amnesia. Rats received lidocaine and anisomycin injections into the amygdala 130 and 120 min, respectively, prior to inhibitory avoidance training. Memory tests 48 h later revealed that lidocaine attenuated anisomycin-induced amnesia. In other rats, in vivo microdialysis was performed at the site of amygdala infusion of lidocaine and anisomycin. As seen previously, anisomycin injections produced large increases in release of norepinephrine in the amygdala. Lidocaine attenuated the anisomycin-induced increase in release of norepinephrine but did not reverse anisomycin inhibition of protein synthesis, as assessed by c-Fos immunohistochemistry. These findings are consistent with past evidence suggesting that anisomycin causes amnesia by initiating abnormal release of neurotransmitters in response to the inhibition of protein synthesis.
当在接近训练时间给药时，蛋白质合成抑制剂，如放线菌酮，会损害随后的记忆。这些发现的一个常见解释是，记忆巩固需要由训练引发的新的蛋白质合成。然而，最近的发现支持了另一种解释，即在注射放线菌酮后，神经递质释放异常增加可能是导致失忆的原因。在本研究中，在注射放线菌酮之前给予局部麻醉剂，试图减轻神经递质的作用，从而减轻由此产生的失忆。大鼠在进行抑制性回避训练之前，分别将利多卡因和放线菌酮注入杏仁核 130 和 120 分钟。48 小时后的记忆测试显示，利多卡因减轻了放线菌酮引起的失忆。在其他大鼠中，在体内微透析在利多卡因和放线菌酮注入杏仁核的部位进行。如前所述，放线菌酮注射会导致杏仁核中去甲肾上腺素释放大量增加。利多卡因减弱了放线菌酮引起的去甲肾上腺素释放增加，但并未逆转放线菌酮对蛋白质合成的抑制作用，这可以通过 c-Fos 免疫组织化学评估。这些发现与过去的证据一致，表明放线菌酮通过在蛋白质合成抑制后引发异常的神经递质释放而导致失忆。
