Feldman J M
Veterans Administration Medical Center, Durham, NC 27710.
Behav Brain Res. 1988 Jul;29(1-2):147-58. doi: 10.1016/0166-4328(88)90062-9.
Obese-hyperglycemic mice (genotype ob/ob) have higher levels of hypothalamic norepinephrine than their normal-weight litter mates. Brain, as well as some other tissues, contains two types of monoamine oxidase (MAO). In this study we evaluated the effect of administering the Type A MAO inhibitor clorgyline (clorg) and the Type B MAO inhibitor pargyline (parg) on food intake. Acute administration of clorg/parg caused a temporary 50-90% decrease in food intake in normal mice, rats, golden, and Chinese hamsters, but did not alter the food intake of obese mice. To determine if alterations in the concentration of brain monoamines played a role in the effect of clorg/parg on food intake in mice, we determined the concentration of serotonin, dopamine, and norepinephrine in their cerebral cortex and hypothalamus after clorg/parg administration. When compared to normal mice, obese mice had a greater concentration of serotonin in their cerebral cortex and norepinephrine in their hypothalamus. As the obese mice had an equal or even greater increase in hypothalamic serotonin and norepinephrine concentration after clorg/parg administration than the normal mice, it is not likely that increased hypothalamic monoamines are responsible for the decreased food intake produced by clorg/parg administration. Obese and normal mice were treated with weekly injections of clorg/parg from 7 to 19 weeks of age. Clorg/parg produced a persistent 12% decrease in food intake and weight in obese, but not normal mice. Although the medication was discontinued at 19 weeks of age, the decrease in food intake and weight of the obese mice persisted until the time of sacrifice at 31-35 weeks. The combination of clorg/parg had a more profound effect on in vivo and in vitro MAO activity than equivalent amounts of the individual MAO inhibitors. Other anorectic agents such as D-amphetamine and fenfluramine had only a trivial in vitro effect on MAO activity.
肥胖高血糖小鼠（基因型ob/ob）下丘脑去甲肾上腺素水平高于其正常体重的同窝小鼠。大脑以及其他一些组织含有两种类型的单胺氧化酶（MAO）。在本研究中，我们评估了给予A型MAO抑制剂氯吉兰（clorg）和B型MAO抑制剂帕吉林（parg）对食物摄入量的影响。急性给予clorg/parg可使正常小鼠、大鼠、金黄地鼠和中国仓鼠的食物摄入量暂时减少50%-90%，但不会改变肥胖小鼠的食物摄入量。为了确定脑单胺浓度的改变是否在clorg/parg对小鼠食物摄入量的影响中起作用，我们在给予clorg/parg后测定了它们大脑皮层和下丘脑的血清素、多巴胺和去甲肾上腺素浓度。与正常小鼠相比，肥胖小鼠大脑皮层中的血清素浓度更高，下丘脑中的去甲肾上腺素浓度更高。由于肥胖小鼠在给予clorg/parg后下丘脑血清素和去甲肾上腺素浓度的增加与正常小鼠相同甚至更大，因此下丘脑单胺增加不太可能是clorg/parg给药导致食物摄入量减少的原因。肥胖和正常小鼠在7至19周龄时每周注射clorg/parg进行治疗。Clorg/parg使肥胖小鼠的食物摄入量和体重持续减少12%，但对正常小鼠没有影响。尽管在19周龄时停止用药，但肥胖小鼠的食物摄入量和体重减少一直持续到31-35周处死时。与等量的单独MAO抑制剂相比，clorg/parg组合对体内和体外MAO活性的影响更为显著。其他厌食剂如右旋苯丙胺和芬氟拉明对MAO活性的体外影响很小。
