Age - related modifications of effects of ketamine and propofol on rat hippocampal acetylcholine release studied by in vivo brain microdialysis

背景：海马胆碱能神经元被认为与学习和记忆有关。目前还没有关于麻醉剂对胆碱能神经递质作用的年龄相关改变的报道。本研究的目的是研究氯胺酮和异丙酚对大鼠海马乙酰胆碱（ACh）释放影响的年龄相关变化。方法：以雄性Wistar幼龄大鼠（2月龄）和成年大鼠（18月龄）为实验对象，在自由活动条件下采用活体脑微透析技术。在最初的三次采集取样后，使用试验药物。HPLC-ECD法测定乙酰胆碱释放量。结果：老龄大鼠海马基底区乙酰胆碱释放量明显低于幼龄大鼠。氯胺酮25mg kg-1 ig使幼龄大鼠海马乙酰胆碱释放量增加到基础释放量的181%，而老龄大鼠相同剂量氯胺酮ig使海马乙酰胆碱释放量增加到基础释放量的229%。另一方面，25 mg kg-1 i.p.异丙酚对幼龄大鼠海马乙酰胆碱释放有抑制作用（抑制39%），对老年大鼠有抑制作用（抑制48%）。尽管异丙酚的最大抑制峰效应在幼龄大鼠和老年大鼠之间没有显著差异，但老年大鼠海马乙酰胆碱释放下降的持续时间比幼龄大鼠长。结论：氯胺酮对老年大鼠海马乙酰胆碱释放的促进作用较年轻大鼠明显。另一方面，异丙酚对幼龄和老年大鼠海马乙酰胆碱释放有抑制作用，衰老过程可能抑制异丙酚诱导的抑制性麻醉状态的恢复能力。

Background : Hippocampal cholinergic neurons are supposed to be involved in learning and memory. There has been no report on age-related modifications of cholinergic neurotransmitter action by anesthetics. The aim of this study was to examine age-related modifications of the effects of ketamine and propofol on rat hippocampal acetylcholine (ACh) release.Methods : The experiments were performed on male Wistar young rats (two months old) and aged rats (18 months old), using in vivo brain microdialysis technique under freely moving condition. After sampling initial three collections, test drugs were administered. The ACh release was determined by HPLC-ECD method.Results : In aged rats, the hippocampal basal ACh release was significantly lower than in young rats. Ketamine 25 mg kg-1 i.p. increased the hippocampal ACh release in young rats to 181% of the basal release, while in aged rats the same dose of ketamine i.p. increased the hippocampal ACh release to 229 % of the basal release. On the other hand, propofol 25 mg kg-1 i.p. produced inhibitory effects on the hippocampal ACh release in young rats (by 39 %) and in aged rats (by 48 %). Although the maximal inhibitory peak effects of propofol did not differ significantly between young and aged rats, decrease of the hippocampal ACh release in aged rats persisted longer than in young rats.Conclusion : Ketamine produced more pronounced facilitatory effects on the hippocampal ACh release in aged rats, as compared to in young rats. On the other hand, propofol has inhibitory effects on the hippocampal ACh release in young and aged rats and aging process may suppress the abilities to recover from inhibitory anaesthetic state induced by propofol.