McCall R B, Clement M E, Harris L T
Cardiovascular Diseases Research, Upjohn Company, Kalamazoo, MI 49001.
Brain Res. 1989 Oct 30;501(1):73-83. doi: 10.1016/0006-8993(89)91028-7.
Previous studies indicate that the selective 5-HT1A agonist, 8-OH DPAT, acts in the central nervous system to inhibit sympathetic nerve activity. Based on the observations that: (1) 8-OH DPAT acts at serotonin (5-HT) autoreceptors to inhibit 5-HT neuronal firing; and (2) medullary 5-HT neurons provide a tonic excitatory input to sympathetic preganglionic neurons, we have hypothesized that 8-OH DPAT produces its sympatholytic effects by inhibiting medullary 5-HT neuronal firing and thereby removing an excitatory input to sympathetic preganglionic neurons. The present study was designed to critically test this hypothesis. The sympatholytic effects of 8-OH DPAT were compared in intact animals and in animals which received large electrolytic lesions in the midline area of the lower brainstem. These lesions extended from the obex rostral through the level of the facial motor nucleus and encompassed the brain stem from the dorsal to the ventral surface. The sympatholytic effect of 8-OH DPAT was identical in intact animals and in animals receiving the lesion. The inhibitory effects of 8-OH DPAT on activity recorded simultaneously from the inferior cardiac sympathetic nerve and from medullospinal 5-HT neurons were determined. Medullary 5-HT neurons were identified using criteria modeled after the electrophysiological and pharmacological characteristics previously described for dorsal raphe 5-HT neurons. Medullary 5-HT neuronal activity was more sensitive to the inhibitory effects of 8-OH DPAT than was sympathetic activity. Indeed, low doses of 8-OH DPAT completely suppressed the firing of medullary 5-HT neurons but had little effect on sympathetic nerve activity. These data fail to support the hypothesis that inhibition of 5-HT neuronal firing is responsible for the central sympatholytic effects of 8-OH DPAT. Rather, the data suggest that 8-OH DPAT acts postsynaptically on 5-HT1A receptors located on central sympathetic neurons to inhibit sympathetic nerve activity.
先前的研究表明，选择性5-羟色胺1A（5-HT1A）激动剂8-羟基二丙胺基四氢萘（8-OH DPAT）在中枢神经系统中发挥作用，抑制交感神经活动。基于以下观察结果：（1）8-OH DPAT作用于5-羟色胺（5-HT）自身受体，抑制5-HT神经元放电；（2）延髓5-HT神经元向交感神经节前神经元提供持续性兴奋性输入，我们推测8-OH DPAT通过抑制延髓5-HT神经元放电，从而消除对交感神经节前神经元的兴奋性输入，产生其抗交感神经作用。本研究旨在严格验证这一假设。在完整动物和在下脑干中线区域接受大面积电解损伤的动物中，比较了8-OH DPAT的抗交感神经作用。这些损伤从延髓尾端向上延伸至面神经运动核水平，涵盖了从脑干背侧到腹侧表面的区域。8-OH DPAT在完整动物和接受损伤的动物中的抗交感神经作用相同。测定了8-OH DPAT对同时记录的心脏下交感神经和延髓脊髓5-HT神经元活动的抑制作用。延髓5-HT神经元是根据先前描述的中缝背核5-HT神经元的电生理和药理学特征建立的标准来鉴定的。延髓5-HT神经元活动对8-OH DPAT的抑制作用比交感神经活动更敏感。事实上，低剂量的8-OH DPAT完全抑制了延髓5-HT神经元的放电，但对交感神经活动几乎没有影响。这些数据不支持5-HT神经元放电的抑制是8-OH DPAT中枢抗交感神经作用的原因这一假设。相反，数据表明8-OH DPAT在突触后作用于位于中枢交感神经元上的5-HT1A受体，以抑制交感神经活动。
