Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada N6A 5C1.
Exp Neurol. 2011 Apr;228(2):259-69. doi: 10.1016/j.expneurol.2011.01.019. Epub 2011 Feb 2.
Acetylcholine in the brain has been associated with consciousness and general anesthesia effects. We tested the hypothesis that the integrity of the nucleus basalis magnocellularis (NBM) affects the response to general anesthetics. Cholinergic neurons in NBM were selectively lesioned by bilateral infusion of 192IgG-saporin in adult, male Long-Evans rats, and control rats were infused with saline. Depletion of choline-acetyltransferase (ChAT)-immunoreactive cells in the NBM and decrease in optical density of acetylcholinesterase (AChE) staining in the frontal and visual cortices confirmed a significant decrease in NBM cholinergic neurons in lesioned as compared to control rats. AChE staining in the hippocampus and ChAT-positive neurons in the medial septum-vertical limb of the diagonal band were not different between lesioned and control rats. When a general anesthetic was administered, lesioned compared to control rats showed significantly longer duration of loss of righting reflex (LORR) after propofol (5 or 10mg/kg i.v.), pentobarbital (20 or 40 mg/kg i.p.) but not halothane (2%). However, the behavioral excitation, as indicated by horizontal movements, induced by halothane was reduced in lesioned as compared to control rats. Reversible inactivation of NBM with GABA(A) receptor agonist muscimol increased slow waves in the neocortex during awake immobility, and prolonged the duration of LORR and loss of tail-pinch response after propofol, pentobarbital and halothane. In summary, lesion of NBM cholinergic neurons or inactivation of the NBM prolonged the LORR response to general anesthetic drugs.
大脑中的乙酰胆碱与意识和全身麻醉效应有关。我们检验了这样一个假设，即基底核大细胞（NBM）的完整性会影响全身麻醉药物的反应。通过在成年雄性 Long-Evans 大鼠双侧输注 192IgG-saporin，选择性地破坏 NBM 中的胆碱能神经元，而对照组大鼠则输注盐水。NBM 中的胆碱乙酰转移酶（ChAT）免疫反应性细胞耗竭和额皮质和视皮质中乙酰胆碱酯酶（AChE）染色的光密度降低证实了损伤大鼠 NBM 胆碱能神经元的明显减少。与损伤大鼠相比，损伤大鼠的海马 AChE 染色和中隔-斜角带垂直支的 ChAT 阳性神经元没有差异。当给予全身麻醉药物时，与对照组大鼠相比，损伤组大鼠在丙泊酚（5 或 10mg/kg 静脉注射）、戊巴比妥（20 或 40mg/kg 腹腔注射）后失去翻正反射（LORR）的持续时间明显更长，但异氟烷（2%）则不然。然而，与对照组大鼠相比，损伤组大鼠对异氟烷引起的水平运动等行为兴奋减少。用 GABA(A)受体激动剂 muscimol 可逆性地失活 NBM，可在清醒不动时增加新皮质中的慢波，并延长丙泊酚、戊巴比妥和异氟烷后 LORR 和尾巴刺痛反应的持续时间。总之，NBM 胆碱能神经元的损伤或 NBM 的失活延长了全身麻醉药物的 LORR 反应。
