Reddy D S, Kulkarni S K
Department of Pharmacology, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Mol Cell Biochem. 1998 Jun;183(1-2):25-38. doi: 10.1023/a:1006815125689.
The nitric oxide (NO) synthase inhibitor NG-monomethyl-L-arginine (N-NMMA) and the competitive substrate for NO synthase L-arginine were used to determine the role of endogenous NO on the behavioral and neuroendocrine responsiveness following systemic corticotrophin in dexamethasone-suppressed rats. Corticotrophin (50-200 mU/kg, s.c.) dose-dependently decreased behavioral activity in the actimeter and produced significant anxiolytic and anti-risk activity in the plus-maze behavior test, without affecting systolic blood pressure. Rats given corticotrophin showed significant increased plasma corticosterone and reduced adrenal ascorbic acid level. These behavioral and adrenal responses of corticotrophin were dose dependently blocked by metyrapone (20 and 50 mg/kg, i.p.), an inhibitor of steroid 11beta-hydroxylase in adrenal and neural tissues that block steroidogenesis. Intracerebroventricular administration of L-NMMA (20 microg/rat in 10 microl) significantly prevented the behavioral hypoactivity and anxiolytic-like responses of corticotrophin without influencing the adrenal responsiveness. The effect of L-NMMA was completely reversed by preadministration of L-arginine (300 mg/kg, i.p.). These results suggest that neuronal nitric oxide pathway plays an important modulating role in the behavioral effects of corticotrophin by mechanisms other than those involving cardiovascular effects.
一氧化氮（NO）合酶抑制剂N-甲基-L-精氨酸（N-NMMA）和NO合酶的竞争性底物L-精氨酸被用于确定内源性NO在全身注射促肾上腺皮质激素后，对地塞米松抑制的大鼠行为和神经内分泌反应性中的作用。促肾上腺皮质激素（50 - 200 mU/kg，皮下注射）剂量依赖性地降低了活动计中的行为活动，并在十字迷宫行为测试中产生了显著的抗焦虑和抗风险活动，而不影响收缩压。给予促肾上腺皮质激素的大鼠血浆皮质酮显著升高，肾上腺抗坏血酸水平降低。促肾上腺皮质激素的这些行为和肾上腺反应被美替拉酮（20和50 mg/kg，腹腔注射）剂量依赖性地阻断，美替拉酮是肾上腺和神经组织中类固醇11β-羟化酶的抑制剂，可阻断类固醇生成。脑室内注射L-NMMA（20 μg/大鼠，10 μl）显著预防了促肾上腺皮质激素的行为活动减退和抗焦虑样反应，而不影响肾上腺反应性。预先给予L-精氨酸（300 mg/kg，腹腔注射）可完全逆转L-NMMA的作用。这些结果表明，神经元一氧化氮途径通过不涉及心血管效应的机制，在促肾上腺皮质激素的行为效应中发挥重要的调节作用。
