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

通过体内脑微透析研究氯胺酮和异丙酚对大鼠海马乙酰胆碱释放影响的年龄相关变化

• 批准号: 09470334
• 负责人: OKUMURA Fukuichiro
• 金额: $ 3.78万
• 依托单位: Yokohama City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470334/
• 关键词: Microdialysis; Acetylcholine; Anesthetics; Propofol; Ketamine; Aging; Hippocampus; 老化

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.

背景：海马胆碱能神经元被认为参与学习和记忆。目前还没有麻醉药对胆碱能神经递质作用的增龄性改变的报道。本研究旨在探讨氯胺酮和异丙酚对大鼠海马乙酰胆碱(ACh)释放的增龄性调节作用。方法：采用Wistar雄性青年大鼠(2月龄)和老年大鼠(18月龄)，在自由活动条件下采用活体脑微透析技术。在对最初的三个样本进行抽样后，进行了测试药物的管理。结果：老年大鼠海马区基础ACh释放量明显低于青年大鼠。氯胺酮25 mg·kg~(-1)ip。使幼年大鼠海马区ACh释放量增加至基础释放量的181%，而老年大鼠腹腔注射相同剂量的氯胺酮。使海马ACh释放量增加至基础释放量的229%。异丙酚25 mg·kg~(-1)ip。对年轻大鼠(39%)和老年大鼠(48%)的海马乙酰胆碱释放有抑制作用。尽管异丙酚的最大抑制峰效应在青年大鼠和老年大鼠之间没有显著差异，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释放的易化作用比青年大鼠更明显。另一方面，异丙酚对青年和老年大鼠海马区ACh释放有抑制作用，衰老过程可能抑制异丙酚诱导的抑制麻醉状态的恢复能力。

项目成果

Kazuo Sato et al.: "Differential effects of ketamine and pentobarbitone on acetylcholine release from the rat hippocampus and striatum" British Journal of Anaesthesia. 77. 381-384 (1996)

Kazuo Sato 等人：“氯胺酮和戊巴比妥对大鼠海马和纹状体乙酰胆碱释放的不同影响”英国麻醉杂志。

Tatsuaki Kikuchi et al.: "Effects of ketamine and pentobarbitone on acetylcholine release from the rat frontal cortex in vivo" British Journal of Anaesthesia. 79. 128-130 (1997)

Tatsuaki Kikuchi 等人：“氯胺酮和戊巴比妥对体内大鼠额叶皮层乙酰胆碱释放的影响”英国麻醉杂志。