Antagonism by NOS inhibition of the behavioral effects of benzodiazepine and GABAA receptor agonists in the mouse elevated plus-maze.
Antagonism by NOS inhibition of the behavioral effects of benzodiazepine and GABAA receptor agonists in the mouse elevated plus-maze.
复制标题
NOS 抑制对苯二氮卓类和 GABAA 受体激动剂在小鼠高架十字迷宫中的行为效应的拮抗作用。
DOI：
10.1038/sj.npp.1300437
复制
发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Quock,RaymondM
中科院分区：
文献类型：
--
作者：
Elfline,GeraldineS;Branda,EmilyM;Babich,Michael;Quock,RaymondM
早先我们暗示一氧化氮（NO）在苯二氮卓类药物的行为效应的调解。由于苯二氮卓类药物通过促进GABA能抑制性神经传递发挥作用，本研究旨在确定直接作用的γ-氨基丁酸A（GABA A）受体激动剂THIP（4，5，6，7-tetrahydroisoxazolo [5，4-c] pyridin-3-ol）是否引起与苯二氮卓类药物相似的行为效应，以及THIP的行为效应是否也是NO依赖性的。当在高架十字迷宫模式中用利血平或THIP激发时，雄性NIH Swiss小鼠表现出剂量相关的开臂活动增加。苯二氮卓类拮抗剂对氯二氮卓诱导的效应敏感，而THIP的效应可被GABA A受体拮抗剂阻断。用NO合成酶（NOS）抑制剂L-N-G-硝基精氨酸预处理可拮抗利血平和THIP的作用;用D-异构体D-N-G-硝基精氨酸（作为NOS抑制剂无活性）进行类似的预处理对利血平和THIP没有影响。这些结果表明，利血平和THIP引起类似的行为效应，在小鼠在高架十字迷宫通过对GABA A受体的不同部分的行动，和NO似乎发挥关键作用，在调解利血平和THIP的行为效应。
Earlier we implicated nitric oxide (NO) in mediation of the behavioral effects of benzodiazepines. Since benzodiazepines work through facilitation of GABAergic inhibitory neurotransmission, this study was designed to determine whether the direct-acting γ-aminobutyric acid A (GABA A) receptor agonist THIP (4, 5, 6, 7-tetrahydroisoxazolo [5, 4-c] pyridin-3-ol) evokes behavioral effects similar to those of benzodiazepines and whether behavioral effects of THIP are also NO dependent. When challenged with either chlordiazepoxide or THIP in an elevated plus-maze paradigm, male NIH Swiss mice exhibited a dose-related increase in open-arm activity. The chlordiazepoxide-induced effects were sensitive to antagonism by a benzodiazepine antagonist, and the effects of THIP were blocked by a GABA A receptor antagonist. Pretreatment with the NO synthase (NOS) inhibitor L-N G-nitro arginine antagonized the effects of both chlordiazepoxide and THIP; similar pretreatment with the D-isomer, D-N G-nitro arginine, which is inactive as an NOS inhibitor, was without effect on chlordiazepoxide and THIP. These findings indicate that chlordiazepoxide and THIP evoke similar behavioral effects in mice in the elevated plus-maze through actions on different parts of the GABA A receptor, and that NO appears to play a key role in mediation of the behavioral effects of both chlordiazepoxide and THIP.