Stricker-Krongrad A, Beck B, Burlet C
INSERM U-308. MRCA. Equipe de Neurobiologie et Physiologie Expérimentales, Nancy, France.
Life Sci. 1996;58(1):PL9-15. doi: 10.1016/0024-3205(95)02260-0.
The presence of a nitric oxide synthetase (NOS) was demonstrated in the rat brain. It has been demonstrated recently that NOS-inhibitors reduce food intake in mammals and this suggest that nitric oxide (NO) might be a physiological mediator involved in the mechanisms controlling feeding behavior. Actually, there is no information about the acute central and peripheral effects of NOS-inhibitors on feeding behavior in obese and lean Zucker rats. That is why we investigated the acute dose-dependent activity of NG-Nitro-Arginine-Methyl-Ester (L-NAME) on food intake and feeding behavior in these rats. When given peripherally in the obese rats, L-NAME produced a dose-dependent decrease in food intake (p<0.001). The calculated MED and the ED 50 were 0.50 mg/kg IP and 3.46 mg/kg IP, respectively. These effects could not be reproduced in the lean Zucker rats whatever the dose used (p=0.59). The anorectic properties of L-NAME were very well translated into the microstructure of the feeding behavior. Time spent to eat (p<0.001), meal duration (p<0.01) and meal number (p<0.01) were reduced in the obese rats. Interestingly, L-NAME produced the same effects in the lean rats, but meal size increased in a compensatory manner. Central administration of L-NAME reproduced the same effects in the obese rats, but lean rats still remained insensitive. Central aminergic and/or peptidergic defects associated with the expression of hyperphagia might explain the differences observed between these lean and the obese animals. These results indicate a role of nitric oxide in the expression of hyperphagia and show that it might be a physiological mediator involved in the mechanisms controlling feeding behavior.
在大鼠脑中已证实存在一氧化氮合酶（NOS）。最近有研究表明，NOS抑制剂可减少哺乳动物的食物摄入量，这表明一氧化氮（NO）可能是参与控制进食行为机制的一种生理介质。实际上，关于NOS抑制剂对肥胖和瘦型 Zucker 大鼠进食行为的急性中枢和外周作用尚无相关信息。这就是我们研究 NG - 硝基 - 精氨酸 - 甲酯（L - NAME）对这些大鼠食物摄入量和进食行为的急性剂量依赖性活性的原因。当外周给予肥胖大鼠L - NAME时，食物摄入量呈剂量依赖性减少（p<0.001）。计算得出的最小有效剂量（MED）和半数有效剂量（ED50）分别为0.50 mg/kg腹腔注射和3.46 mg/kg腹腔注射。无论使用何种剂量，这些作用在瘦型 Zucker 大鼠中均无法重现（p = 0.59）。L - NAME的厌食特性很好地反映在进食行为的微观结构上。肥胖大鼠的进食时间（p<0.001）、餐次持续时间（p<0.01）和餐数（p<0.01）均减少。有趣的是，L - NAME在瘦型大鼠中产生了相同的效果，但餐量以补偿性方式增加。向中枢给予L - NAME在肥胖大鼠中重现了相同的效果，但瘦型大鼠仍然不敏感。与贪食表达相关的中枢胺能和/或肽能缺陷可能解释了这些瘦型和肥胖动物之间观察到的差异。这些结果表明一氧化氮在贪食表达中起作用，并表明它可能是参与控制进食行为机制的一种生理介质。
