Department of Physiology and Pharmacology, The University of Western Ontario, London, Ontario, Canada.
Anesthesiology. 2011 Jul;115(1):36-43. doi: 10.1097/ALN.0b013e3182207655.
The brain histaminergic system plays a critical role in maintenance of arousal. Previous studies suggest that histaminergic neurotransmission might be a potential mediator of general anesthetic actions. However, it is not clear whether histaminergic tuberomamillary nucleus (TMN) is necessarily involved in the sedative/hypnotic effects of general anesthetics.
Male Long Evans rats underwent either TMN orexin-saporin/sham lesion or implantation of intracerebroventricular cannula 2 weeks before the experiment. The behavioral endpoint of loss of righting reflex was used to assess the hypnotic property of isoflurane, propofol, pentobarbital, and ketamine in animals. Histaminergic cell loss was assessed by adenosine deaminase expression in the TMN using immunohistochemistry.
Rats with bilateral TMN orexin-saporin lesion induced an average 72% loss of histaminergic cells compared with sham-lesion rats. TMN orexin-saporin lesion or intracerebroventricular administration of triprolidine (an H1 receptor antagonist) decreased the 50% effective concentration for loss of righting reflex value and prolonged emergence time to isoflurane anesthesia. However, TMN orexin-saporin lesion had no significant effect on the anesthetic sensitivity to propofol, pentobarbital, and ketamine.
These findings suggest a role of the TMN histaminergic neurons in modulating isoflurane anesthesia and that the neural circuits for isoflurane-induced hypnosis may differ from those of γ-aminobutyric acid-mediated anesthetics and ketamine.
脑组胺能系统在维持觉醒中起着关键作用。先前的研究表明，组胺能神经传递可能是全身麻醉作用的潜在介质。然而，组胺能结节乳头核（TMN）是否必然参与全身麻醉的镇静/催眠作用尚不清楚。
雄性长爪沙鼠在实验前 2 周接受 TMN 食欲素-蜂毒素/假损伤或侧脑室植入术。使用翻正反射丧失的行为终点来评估异氟烷、异丙酚、戊巴比妥和氯胺酮在动物中的催眠特性。通过 TMN 中腺苷脱氨酶表达的免疫组织化学评估组胺能细胞的丧失。
与假损伤大鼠相比，双侧 TMN 食欲素-蜂毒素损伤大鼠的组胺能细胞平均丧失 72%。TMN 食欲素-蜂毒素损伤或侧脑室给予曲普利啶（H1 受体拮抗剂）降低了异氟烷麻醉中翻正反射丧失的 50%有效浓度值，并延长了苏醒时间。然而，TMN 食欲素-蜂毒素损伤对异丙酚、戊巴比妥和氯胺酮的麻醉敏感性没有显著影响。
这些发现表明 TMN 组胺能神经元在调节异氟烷麻醉中起作用，并且异氟烷诱导催眠的神经回路可能与γ-氨基丁酸介导的麻醉剂和氯胺酮的神经回路不同。
