Whittington Robert A, Virág László
Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, 622 West 168 Street PH 5, New York, New York 10032, USA.
Anesth Analg. 2006 Jul;103(1):92-8, table of contents. doi: 10.1213/01.ane.0000221488.48352.61.
The serotonergic system may play a role during general anesthesia. Furthermore, alterations in serotonergic neurotransmission in the hippocampus have been linked to depression and anxiety as well as to changes in arousal and cognition. Little is known about the effects of volatile anesthetics on hippocampal serotonin (5-HT) levels. In this study we examined the effects of isoflurane on hippocampal 5-HT levels in mice. Adult male 129/SvEv mice were exposed to either isoflurane 1 or 1.5 minimum alveolar concentration (MAC) both in 40% O2 in air or to 40% O2 in air alone (control) for a period of 80 min, and hippocampal 5-HT levels were measured by microdialysis coupled with high performance liquid chromatography. Within 20-40 min of administration, both doses of isoflurane similarly produced a significant decrease in hippocampal 5-HT to 41.5% +/- 11.0% and 36.4% +/- 13.9% of the baseline level in the isoflurane 1 MAC and 1.5 MAC groups, respectively. Furthermore, when additional dialysates were obtained on termination of anesthesia in the isoflurane 1.5 MAC group, the decrease in extracellular 5-HT levels persisted for several hours. To determine if isoflurane-induced changes in extracellular 5-HT involve the serotonin transporter (SERT), similar microdialysis studies were performed in C57BL/6 wild-type (SERT +/+) and homozygous SERT knockout (SERT -/-) mice exposed to either 1 MAC isoflurane in 40% O2 in air or to 40% O2 in air alone for a period of 80 min. Isoflurane produced a significant decrease in hippocampal 5-HT in SERT +/+ and SERT -/-, and this decrease was larger in SERT -/- compared with SERT +/+: to 22.4% +/- 8.5% versus 50.2% +/- 17.4% of the baseline 5-HT level, respectively. These data suggest that isoflurane produces a decrease in hippocampal 5-HT, independent of SERT function.
血清素能系统可能在全身麻醉过程中发挥作用。此外，海马体中血清素能神经传递的改变与抑郁、焦虑以及觉醒和认知的变化有关。关于挥发性麻醉剂对海马体血清素（5-羟色胺，5-HT）水平的影响，目前所知甚少。在本研究中，我们检测了异氟烷对小鼠海马体5-HT水平的影响。成年雄性129/SvEv小鼠在含40%氧气的空气中暴露于1或1.5最低肺泡浓度（MAC）的异氟烷中，或仅暴露于含40%氧气的空气中（对照组）80分钟，然后通过微透析结合高效液相色谱法测量海马体5-HT水平。给药后20至40分钟内，两个剂量的异氟烷均同样使海马体5-HT显著降低，在异氟烷1 MAC组和1.5 MAC组中分别降至基线水平的41.5%±11.0%和36.4%±13.9%。此外，在异氟烷1.5 MAC组麻醉结束时获取额外的透析液时，细胞外5-HT水平的降低持续了数小时。为了确定异氟烷引起的细胞外5-HT变化是否涉及血清素转运体（SERT），我们在C57BL/6野生型（SERT +/+）和纯合SERT基因敲除（SERT -/-）小鼠中进行了类似的微透析研究，这些小鼠在含40%氧气的空气中暴露于1 MAC异氟烷或仅暴露于含40%氧气的空气中80分钟。异氟烷使SERT +/+和SERT -/-小鼠的海马体5-HT显著降低，且SERT -/-小鼠的降低幅度大于SERT +/+小鼠：分别降至基线5-HT水平的22.4%±8.5%和50.2%±17.4%。这些数据表明，异氟烷可使海马体5-HT降低，且与SERT功能无关。
