Heinrichs S C, Koob G F
Scripps Research Institute, Department of Neuropharmacology, La Jolla, CA 92037.
Psychopharmacology (Berl). 1992;109(1-2):177-84. doi: 10.1007/BF02245497.
In order to evaluate the action of central nervous system Corticotropin-Releasing Factor (CRF) in the control of feeding behavior the present studies employed a dietary self-selection task sensitive both to overall appetite as well as preferential intake of familiar versus unfamiliar foods. Prior to the diet selection test, one group of nutritionally stressed animals was fed a protein deficient diet in order to increase the preference for unfamiliar foods relative to nutritionally replete subjects. Both CRF (0.05 and 0.5 micrograms ICV) and physical restraint (30 min) attenuated selectively the consumption of a novel food choice by deficient animals without affecting concurrent intake of familiar food. Further, CRF administration did not alter water intake or consumption of either diet by the replete control group suggesting that the peptide produced a stress dependent, enhanced response to novelty without a general effect on appetite. The CRF antagonist, alpha-helical CRF9-41 (1, 5 and 25 micrograms ICV), increased familiar diet consumption in nutritionally deficient subjects without affecting the self-selection pattern or replete controls. Chlordiazepoxide (5 mg/kg) also increased selectively the intake of familiar food suggesting that this action is the anxiolytic complement of the effect of stress in this paradigm. The CRF antagonist (5 and 25 micrograms) reversed the anorexia produced by CRF (0.5 micrograms) as well as that induced by restraint stress. These results favor a direct role for endogenous CRF systems in coordinating the behavioral responses to dietary stress.
为了评估中枢神经系统促肾上腺皮质激素释放因子(CRF)在控制摄食行为中的作用,本研究采用了一种饮食自我选择任务,该任务对总体食欲以及熟悉食物与不熟悉食物的偏好性摄入均敏感。在饮食选择测试之前,一组营养应激动物被喂食蛋白质缺乏饮食,以相对于营养充足的动物增加对不熟悉食物的偏好。CRF(0.05和0.5微克,脑室内注射)和身体束缚(30分钟)均选择性地减弱了缺乏组动物对新食物选择的消耗,而不影响同时对熟悉食物的摄入。此外,给予CRF并未改变营养充足对照组动物的水摄入量或两种饮食的消耗量,这表明该肽产生了一种应激依赖性的、对新事物增强的反应,而对食欲没有普遍影响。CRF拮抗剂α-螺旋CRF9-41(1、5和25微克,脑室内注射)增加了营养缺乏动物对熟悉饮食的消耗,而不影响自我选择模式或营养充足的对照组。氯氮卓(5毫克/千克)也选择性地增加了对熟悉食物的摄入,表明这种作用是该范式中应激效应的抗焦虑补充。CRF拮抗剂(5和25微克)逆转了CRF(0.5微克)以及束缚应激诱导的厌食症。这些结果支持内源性CRF系统在协调对饮食应激的行为反应中起直接作用。