Honda M, Ono H
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Science University of Tokyo, Japan.
Eur J Pharmacol. 1999 Jun 4;373(2-3):171-9. doi: 10.1016/s0014-2999(99)00284-8.
We examined the effects of (R)- and (S)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT) on the monosynaptic spinal reflex in rats. In intact rats, (R)-8-OH-DPAT (10 microg/kg, i.v.) enhanced the amplitude of the monosynaptic reflex, whereas at 100 microg/kg, it reduced the amplitude. (S)-8-OH-DPAT enhanced the monosynaptic reflex dose-dependently. In spinalized rats, (R)-8-OH-DPAT produced dose-dependent inhibition, but the (S)-enantiomer did not affect the monosynaptic reflex. Pretreatment with spiroxatrine or 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]-piperazine (NAN-190) inhibited (R)-8-OH-DPAT-induced monosynaptic reflex enhancement in intact rats, as did 5-hydroxytryptamine (5-HT) depletion. Ketanserin reduced the effect of (R)-8-OH-DPAT. These pretreatment regimens had no effect on the monosynaptic reflex depression produced by the (R)-enantiomer in intact and spinalized rats. Pretreatment with prazosin inhibited (S)-8-OH-DPAT-induced monosynaptic reflex enhancement in intact rats, as did noradrenaline and 5-HT depletion. These results suggest that supraspinal 5-HT1A receptors and the descending serotonergic system are involved in the stimulatory effect of (R)-8-OH-DPAT on the monosynaptic reflex, while both the descending serotonergic and noradrenergic systems, the latter acting via alpha1-adrenoceptors, are involved in the effect of the (S)-enantiomer on this reflex.
我们研究了（R）-和（S）-8-羟基-2-（二正丙基氨基）四氢萘氢溴酸盐（8-OH-DPAT）对大鼠单突触脊髓反射的影响。在完整大鼠中，（R）-8-OH-DPAT（10微克/千克，静脉注射）增强了单突触反射的幅度，而在100微克/千克时则降低了幅度。（S）-8-OH-DPAT剂量依赖性地增强单突触反射。在脊髓横断大鼠中，（R）-8-OH-DPAT产生剂量依赖性抑制，但（S）-对映体不影响单突触反射。用螺沙群或1-（2-甲氧基苯基）-4-[4-（2-邻苯二甲酰亚氨基）丁基]-哌嗪（NAN-190）预处理可抑制完整大鼠中（R）-8-OH-DPAT诱导的单突触反射增强，5-羟色胺（5-HT）耗竭也有此作用。酮色林降低了（R）-8-OH-DPAT的作用。这些预处理方案对完整和脊髓横断大鼠中（R）-对映体产生的单突触反射抑制无影响。用哌唑嗪预处理可抑制完整大鼠中（S）-8-OH-DPAT诱导的单突触反射增强，去甲肾上腺素和5-HT耗竭也有此作用。这些结果表明，脊髓上5-HT1A受体和下行5-羟色胺能系统参与了（R）-8-OH-DPAT对单突触反射的刺激作用，而下行5-羟色胺能和去甲肾上腺素能系统，后者通过α1-肾上腺素受体起作用，参与了（S）-对映体对该反射的作用。
