Smith J C, Whitton P S
Department of Pharmacology, The School of Pharmacy, 29-39 Brunswick Square, WC1N 1AX, London, UK.
Neurosci Lett. 2000 Sep 8;291(1):5-8. doi: 10.1016/s0304-3940(00)01378-1.
The role of nitric oxide (NO) in N-methyl-D-aspartate (NMDA)-regulated release of 5-hydroxytryptamine (5-HT) in the frontal cortex and raphe nuclei of freely moving rats has been studied using microdialysis with dual probes, one in each region of the same animal. In order to do this the selective neuronal nitric oxide synthase (nNOS) inhibitor 7-nitroindazole (7-NI; 1 mM) and the NO donor S-nitroso-N-penicillamine (SNAP; 500 microM-5 mM) were used. All drugs were infused into the raphe via the dialysis probe. NMDA showed an inverse concentration effect on 5-HT release in the raphe with 25 microM decreasing 5-HT release and 100 microM increasing release. At the same time the converse effect was seen in the frontal cortex. Co-infusion of 7-NI abolished the effect of 100 microM but not 25 microM NMDA. 7-NI given alone decreased raphe 5-HT release with a concomitant increase being seen in the frontal cortex. Low concentrations of SNAP infused into the raphe were found to decrease 5HT release locally but increase release in the frontal cortex. In contrast the highest concentration of SNAP used was found to have the opposite effect in both brain regions. These data suggest that NO plays a role in mediating both basal and NMDA-evoked changes in serotonergic transmission between the raphe and frontal cortex.
利用双探针微透析技术，研究了一氧化氮（NO）在自由活动大鼠额叶皮质和中缝核中对N-甲基-D-天冬氨酸（NMDA）调节的5-羟色胺（5-HT）释放的作用，同一动物的每个区域各放置一个探针。为此，使用了选择性神经元型一氧化氮合酶（nNOS）抑制剂7-硝基吲唑（7-NI；1 mM）和NO供体S-亚硝基-N-青霉胺（SNAP；500 microM - 5 mM）。所有药物均通过透析探针注入中缝核。NMDA对中缝核中5-HT释放呈现相反的浓度效应，25 microM时降低5-HT释放，100 microM时增加释放。同时，在额叶皮质观察到相反的效应。共同注入7-NI消除了100 microM NMDA的效应，但未消除25 microM NMDA的效应。单独给予7-NI可降低中缝核中5-HT释放，同时额叶皮质中5-HT释放增加。发现注入中缝核的低浓度SNAP可局部降低5-HT释放，但增加额叶皮质中的释放。相反，所使用的最高浓度SNAP在两个脑区均产生相反的效应。这些数据表明，NO在介导中缝核与额叶皮质之间5-羟色胺能传递的基础变化和NMDA诱发的变化中均发挥作用。
