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参与学习和记忆。目前还没有关于麻醉药对胆碱能神经递质作用的年龄相关性改变的报道。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）释放的影响的年龄相关性修改方法：实验在自由活动条件下，采用在体脑微透析技术，在雄性Wistar青年大鼠（2月龄）和老年大鼠（18月龄）上进行。在对最初三次采集进行采样后，给予试验药物。结果：老年大鼠海马基础ACh释放量明显低于青年大鼠。氯胺酮25 mg kg-1 ip使年轻大鼠海马ACh释放增加至基础释放的181%，而相同剂量的氯胺酮ip使老年大鼠海马ACh释放增加至基础释放的229%。另一方面，丙泊酚25 mg kg-1 ip对年轻大鼠（39%）和老年大鼠（48%）的海马ACh释放产生抑制作用。虽然丙泊酚的最大抑制峰效应在青年和老年大鼠之间没有显着差异，但老年大鼠海马ACh释放的减少持续时间长于青年大鼠。结论：氯胺酮对老年大鼠海马ACh释放产生更明显的易化作用，与青年大鼠相比。另一方面，丙泊酚对青年和老年大鼠海马ACh释放均有抑制作用，衰老过程可能抑制丙泊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.