可卡因对外侧缰核神经元的作用及机制初探

EFFECTS AND POSSIBLE MECHANISM OF COCAINE ON THE NEURONS OF LATERAL HABENULAR NUCLEUS

目的:探讨可卡因对外侧缰核神经元的作用及可能机制。方法:腹腔注射可卡因,观察内、外侧缰核神经元c-Fos蛋白的表达;在外侧缰核微电泳可卡因,观察其痛相关神经元自发及痛诱发放电的改变;应用全细胞膜片钳技术观察可卡因对外侧缰核神经元延迟整流K+电流的影响。结果:①可卡因明显增加外侧缰核c-Fos蛋白表达,但不明显增加内侧缰核c-Fos蛋白表达。②微电泳可卡因至外侧缰核,引起外侧缰核痛兴奋神经元放电增加和痛诱发反应增强,痛抑制神经元放电减少和痛诱发反应减弱。③膜片钳研究显示,可卡因抑制外侧缰核延迟整流K+通道,导致K+电流减少。结论:外侧缰核神经元对可卡因有较高的敏感性,可卡因能兴奋多数外侧缰核神经元,可能是由于其抑制神经元延迟整流K+通道开放产生的。

To investigate the effects and the possible mechanism of cocaine on the neurons of lateral habenular nucleus（LHb）. Methods： We observed the effects on c-Fos protein expression in lateral habenular nucleus and medial habenular nucleus after injecting cocaine into a belly cavity and spontaneous and evoked discharge of pain-correlative unit through iontophoresis of cocaine into LHb. The delayed rectifier K^＋ current was recorded in the acute isolated LHb neuron in whole-cell mode. Results： （1）The c-Fos protein expression was increased by cocaine treatment in LHb, but little effect in MHb. （2）Iontophoresis of cocaine into LHb increased the discharges of pain excitation unit and enhanced excitation response to noxious stimulation, but it decreased the discharges of pain inhibition unit and its responses to noxious stimulation in LHb. （3）Cocaine inhibited the delayed rectifier K^＋ current. Conclusion： Cocaine can excite the LHb and increase its sensitivity. The probable mechanism is that cocaine inhibits the delayed rectifier K^＋ channels.