Neuroethological analysis of memory retention in conditioned taste aversion.

众所周知，丙泊酚等静脉麻醉剂会导致顺行性和逆行性健忘症。在以前的工作中，这些麻醉剂被报道不会影响条件味觉厌恶(CTA)的获得，在条件刺激(CS)呈现之前使用它们。另一方面，去甲肾上腺素系统被认为在记忆保持中起着重要作用。因此，我们研究了在CS和无条件刺激(US)之间应用异丙酚对CTA保留的影响。异丙酚在所考察的所有浓度下不影响CTA的获得。然而，CTA的保留被它们剂量依赖性地抑制。α2阻滞剂育亨宾也显著削弱了CTA的保留。这些结果表明，低浓度异丙酚影响包括α2去甲肾上腺素能受体在内的CTA记忆保持机制。来自近交系C57BL/6的小鼠也得到了类似的结果，这表明小鼠在情绪学习和记忆系统中对异丙酚有一个共同的敏感部位。我们试图利用一个即刻早期基因CFos免疫反应(Fos-IR)作为神经元激活的标记蛋白，确定异丙酚在大脑中的接受部位。αα灌流1h后，比较异丙酚组(异丙酚组)和生理盐水对照组在味觉第二中枢、臂旁核、丘脑前核、杏仁核和大脑皮层味觉区(岛叶皮质)的Fos-IR。我们发现，Fos-IR在杏仁基底外侧核有增加的趋势，尽管在所有被检查的脑区没有显著差异。这些结果表明，杏仁核在CTAM的保留和获得中起着重要的作用。

Intravenous anesthetics such as propofol are known to induce antero- and retrograde amnesia. In previous works, these anesthetics have been reported not to affect the acquisition of conditioned taste aversion(CTA) by their application prior to the presentation of conditioned stimulus(CS). On the other hand, the noradrenergic system is thought to play an important role for the memory retention. Therefore, we examined the effect of propofol applied between CS and unconditioned stimulus(US) on retention of CTA. Propofol did not affect the acquisition of CTA in all concentrations examined. However, the retention of CTA was dose-dependently suppressed by them. An alpha2 blocker, yohimbine, also remarkably impaired the retention of CTA. These results suggest that low concentrations of propofol affect the CTA memory retention mechanism including alpha2 noradrenergic receptors. The similar results were obtained with mice from a mouse inbred strain, C57BL/6,suggesting that mice have a common site sensitive to propofol in the emotional learning and memory system to rats.We tried to identify the receptive site of propofol in the brain, using an immediately early gene, cFos immunoreactivity (Fos-IR) as a maker protein for neuronal activation. The mice brain was fixed by transcardial α α perfusion 1 hr after CTA acquisition and Fos-IR of a group injected with propofol (propofol group) was compared to that of a control group injected with physiological saline at several brain area including the secondary center of gustatory sense, parabrachial nucleus(PBN), the anterior nuclei of thalamus, the amygdala and the cerebral cortex gustatory area (insular cortex). We found that Fos-IR tend to increase in the basolateral amygdala, in spite of no significant difference in all the brain area examined. These results suggest that the amygdala plays important roles on the retention as well as the acquisition of CTAM.