de la Garza R, Freedman R, Hoffer J
Veterans Administration Medical Center, Denver, Colorado 80262.
Neuropharmacology. 1989 May;28(5):495-501. doi: 10.1016/0028-3908(89)90085-3.
The specificity and pharmacological characteristics of the effects of local administration of nicotine on cerebellar Purkinje cells in the rat were examined electrophysiologically. Local application of nicotine, whether by pressure-ejection or by iontophoresis, depressed the spontaneous discharge of Purkinje neurons in a reversible and dose-dependent manner. This action could not be mimicked by local application of vehicle alone. The inhibitory effects of (-)-nicotine were several-fold more potent than that of the (+)-enantiomer. Systemic administration of the ganglion blocker mecamylamine reliably and reproducibly antagonized the nicotine-induced inhibitions of Purkinje cells whereas nicotine-induced excitation of interneurons was not altered. Local pressure-ejection of mecamylamine also antagonized the inhibitory actions of nicotine, administered by iontophoresis. Since the central effects of nicotine on behavior are stereospecific and sensitive to mecamylamine, the data in this study further support the hypothesis that the actions of nicotine on Purkinje neurons are mediated by ganglionic-like receptors. These findings also suggest that the Purkinje cell may serve as a good cellular model for studies on central pharmacology of nicotine.
采用电生理学方法研究了大鼠小脑浦肯野细胞局部给予尼古丁的作用的特异性和药理学特性。无论是通过压力喷射还是离子导入局部应用尼古丁，均可使浦肯野神经元的自发放电以可逆且剂量依赖的方式受到抑制。单独局部应用载体不能模拟这种作用。（-）-尼古丁的抑制作用比（+）-对映体强几倍。全身给予神经节阻滞剂美加明可可靠且可重复地拮抗尼古丁诱导的浦肯野细胞抑制作用，而尼古丁诱导的中间神经元兴奋未改变。局部压力喷射美加明也可拮抗离子导入给予的尼古丁的抑制作用。由于尼古丁对行为的中枢作用具有立体特异性且对美加明敏感，本研究中的数据进一步支持了尼古丁对浦肯野神经元的作用是由类神经节受体介导的这一假说。这些发现还表明，浦肯野细胞可能是研究尼古丁中枢药理学的良好细胞模型。
