Tersigni T J, Rosenberg H C
Department of Pharmacology, Medical College of Ohio, Toledo 43699-0008, USA.
Brain Res. 1996 Sep 16;733(2):184-92. doi: 10.1016/0006-8993(96)00533-1.
This study tested the hypothesis that cannabinoid agonists, applied locally into the pars reticulata of substantia nigra (SNpr), could modulate striatonigral transmission, without affecting the response of SNpr neurons to iontophoretically-applied GABA. Multibarreled glass capillary electrode assemblies were used for extracellular recording of the spontaneous electrical activity of single SNpr cells in anesthetized rats. Local pressure ejection of the cannabinoid agonists Win 55212-2 (WIN2) and CP 55940 increased SNpr spontaneous firing rate by 13-46%, similar to the effects of systemic injections. Neither WIN2 nor CP 55940 had an effect on the slowing of SNpr neuron activity in response to iontophoretic GABA. Local pressure application of Win 55212-3 (the much less active enantiomer of WIN2) produced an insignificant decrease in SNpr firing rate. Similarly, locally applied vehicle (45% 2-hydroxypropyl-beta-cyclodextrin) produced insignificant decreases in SNpr firing. A second application of cannabinoid agonist produced a much smaller effect, suggesting desensitization. Increasing the interval between CP 55940 applications to 45 min showed recovery of sensitivity to the agonist. Local application of the cannabinoid antagonist, SR 141716A, significantly decreased spontaneous cell firing by 34%. CP 55940, when given immediately following or concurrently with the antagonist application failed to produce the expected increase in discharge rate over baseline. A second application of CP 55940 45 min later produced a 26% increase in firing rate. Bicuculline methiodide (BMI) was applied locally causing a significant increase in SNpr cell firing. CP 55940, when locally administered concurrently with bicuculline methiodide, had no further effect on the firing rate of the cell. Based on the reported presynaptic localization of cannabinoid receptors in SNpr, these findings suggest that cannabinoids act within the SNpr to modulate striatonigral neurotransmission presynaptically. The effect of SR 141716A suggests that an endogenous cannabinoid may mediate striato-nigral transmission.
将大麻素激动剂局部应用于黑质网状部（SNpr），可调节纹状体黑质投射，而不影响SNpr神经元对离子导入GABA的反应。多管玻璃微电极组件用于在麻醉大鼠中细胞外记录单个SNpr细胞的自发电活动。大麻素激动剂Win 55212-2（WIN2）和CP 55940的局部压力注射使SNpr自发放电率提高了13%-46%，与全身注射的效果相似。WIN2和CP 55940均未对SNpr神经元对离子导入GABA的活动减慢产生影响。局部压力应用Win 55212-3（WIN2活性低得多的对映体）使SNpr放电率出现不显著的降低。同样，局部应用载体（45% 2-羟丙基-β-环糊精）使SNpr放电出现不显著的降低。第二次应用大麻素激动剂产生的效果要小得多，提示脱敏。将CP 55940应用之间的间隔延长至45分钟显示对激动剂的敏感性恢复。局部应用大麻素拮抗剂SR 141716A使自发放电显著降低34%。CP 55940在拮抗剂应用后立即或同时给予时，未能使放电率比基线水平产生预期的增加。45分钟后第二次应用CP 55940使放电率增加26%。局部应用荷包牡丹碱甲碘化物（BMI）使SNpr细胞放电显著增加。CP 55940在与荷包牡丹碱甲碘化物同时局部给药时，对细胞放电率没有进一步影响。基于报道的SNpr中大麻素受体的突触前定位，这些发现表明大麻素在SNpr内起作用，以突触前方式调节纹状体黑质神经传递。SR 141716A的作用表明内源性大麻素可能介导纹状体-黑质传递。
