Pozzi L, Trabace L, Invernizzi R, Samanin R
Istituto di Ricerche Farmacologiche, Mario Negri, Milan, Italy.
Brain Res. 1995 Sep 18;692(1-2):265-8. doi: 10.1016/0006-8993(95)00595-h.
GR-113808, a potent and selective 5-HT4 receptor antagonist, was infused through a microdialysis probe into the striatum and nucleus accumbens of awake rats, and basal and morphine-stimulated extracellular concentrations of dopamine (DA) were measured in these regions. At 1 and 10 microM GR-113808 did not affect the extracellular concentrations of DA in either region and 100 microM significantly reduced dialysate DA only in the striatum. A subcutaneous dose of 5 mg/kg morphine significantly raised extracellular concentrations of DA in the striatum and nucleus accumbens from 60 to 120 min after injection and the effect was not modified by 10 microM GR-113808 infused through the probe 20 min before and for 60 min after morphine. Bilateral injections of GR-113808 (1, 2.5 and 10 micrograms/0.5 microliter) in the substantia nigra pars compacta did not affect dialysate DA in the striatum, except for a significant increase 120 min after the injection of 10 micrograms but the highest dose of GR-113808 prevented the increase of striatal DA caused by 5 mg/kg morphine s.c. The results suggest that 5-HT4 receptors in the substantia nigra modulate the activity of the dopaminergic nigrostriatal system only when the neurons are activated.
强效选择性5-羟色胺4（5-HT4）受体拮抗剂GR-113808通过微透析探针注入清醒大鼠的纹状体和伏隔核，测定这些区域多巴胺（DA）的基础和吗啡刺激下的细胞外浓度。1和10微摩尔的GR-113808对任一区域的DA细胞外浓度均无影响，而100微摩尔仅使纹状体中的透析液DA显著降低。皮下注射5毫克/千克吗啡可使注射后60至120分钟纹状体和伏隔核中的DA细胞外浓度显著升高，且在吗啡注射前20分钟及注射后60分钟通过探针注入10微摩尔GR-113808并不会改变这种作用。在黑质致密部双侧注射GR-113808（1、2.5和10微克/0.5微升）对纹状体中的透析液DA无影响，不过注射10微克后120分钟有显著升高，但最高剂量的GR-113808可阻止皮下注射5毫克/千克吗啡引起的纹状体DA升高。结果表明，黑质中的5-HT4受体仅在神经元被激活时调节多巴胺能黑质纹状体系统的活性。
