Hiner B C, Mauk M D, Peroutka S J, Kocsis J D
Department of Neurology, Yale University School of Medicine, New Haven, CT 06520.
Brain Res. 1988 Sep 27;461(1):1-9. doi: 10.1016/0006-8993(88)90719-6.
The effects of serotonin (5-hydroxytryptamine; 5-HT), and the novel anxiolytics buspirone, 8-OH-DPAT (8-hydroxy-2-[N,N-dipropylamino]-tetralin) and ipsapirone (TVXQ 7821, 2-[4-[4-[2-pyrimidinyl]-1-piperazinyl] butyl]-1,2-benzisothiazol-3[2H]one-1,1-dioxide-hydrochloride) on fiber excitability were studied in three axon systems; hippocampal Schaffer collateral fibers, cerebellar parallel fibers, and sciatic nerves. In the hippocampus, application of buspirone, 8-OH-DPAT and ipsapirone resulted in reversible, dose-dependent reductions in the amplitude and conduction velocity of action potentials recorded from presynaptic afferent fibers. Although these agents bind to 5-HT1A receptors, 5-HT application, even at very high (1 mM) concentrations, did not alter axonal responses. This suggests that buspirone, 8-OH-DPAT and ipsapirone exert an action independent of a serotonergic mechanism. Similar effects were observed on the cerebellar parallel fibers although the cerebellum does not have an appreciable number of 5-HT1A receptors. To examine the generalized effects of these agents on nerve excitability, rat sciatic compound action potentials were studied with sucrose gap recordings. Whereas 5-HT, 8-OH-DPAT and ipsapirone had no effects even at high concentrations (1 mM), application of buspirone led to reversible decrement of the responses without appreciable change in membrane potential. These results indicate that buspirone, 8-OH-DPAT and ipsapirone have actions on the excitability of hippocampal and cerebellar neurons independent of serotonergic mechanisms. Moreover, buspirone, but not 8-OH-DPAT or ipsapirone, produces decreased sciatic nerve excitability. NS 20393
研究了血清素（5-羟色胺；5-HT）以及新型抗焦虑药丁螺环酮、8-OH-DPAT（8-羟基-2-[N,N-二丙基氨基]-四氢萘）和伊沙匹隆（TVXQ 7821，2-[4-[4-[2-嘧啶基]-1-哌嗪基]丁基]-1,2-苯并异噻唑-3[2H]酮-1,1-二氧化物-盐酸盐）对三种轴突系统纤维兴奋性的影响，这三种轴突系统分别是海马体的谢弗侧支纤维、小脑的平行纤维和坐骨神经。在海马体中，应用丁螺环酮、8-OH-DPAT和伊沙匹隆会导致从突触前传入纤维记录到的动作电位幅度和传导速度出现可逆的、剂量依赖性降低。尽管这些药物与5-HT1A受体结合，但即使在非常高的（1 mM）浓度下应用血清素，也不会改变轴突反应。这表明丁螺环酮、8-OH-DPAT和伊沙匹隆发挥的作用独立于血清素能机制。在小脑平行纤维上也观察到了类似的效果，尽管小脑中没有相当数量的5-HT1A受体。为了研究这些药物对神经兴奋性的普遍影响，用蔗糖间隙记录法研究了大鼠坐骨神经复合动作电位。尽管血清素、8-OH-DPAT和伊沙匹隆即使在高浓度（1 mM）下也没有影响，但应用丁螺环酮会导致反应可逆性降低，且膜电位没有明显变化。这些结果表明，丁螺环酮、8-OH-DPAT和伊沙匹隆对海马体和小脑神经元兴奋性的作用独立于血清素能机制。此外，丁螺环酮会降低坐骨神经兴奋性，而8-OH-DPAT或伊沙匹隆则不会。NS 20393
