Callahan M F, Beales M, Oltmans G A
Pharmacol Biochem Behav. 1984 Apr;20(4):591-9. doi: 10.1016/0091-3057(84)90309-5.
Multiple behavioral and neurochemical abnormalities are found in the genetically obese mouse, obob , including hyperphagia, elevated hypothalamic norepinephrine (NE) levels, and increases alpha-1 receptor density. The obese mutant also responds abnormally to neuropharmacological agents. In the current study the alpha-2 receptor blockers yohimbine and rauwolscine were administered to food-restricted (6-hour food access) obob and lean mice. Yohimbine and rauwolscine significantly reduced the 3- and 6-hour food intake of both obob and lean mice. The obob mice were, however, more sensitive to this anorectic effect than lean mice. Effective anorectic doses of yohimbine did not affect water intake in water-deprived lean mice, suggesting a specific effect of the drug upon food intake. Low doses (50 and 100 micrograms) of the alpha-2 agonist clonidine increased the 1-hour food intake of obob mice, but did not affect the food intake of lean mice. No differences were found between obob and lean mice in the number of alpha-receptors in the hypothalamus. The results suggest that modification of NE release by manipulation of alpha-2 receptor can alter food intake, and that the obob mutant is particularly sensitive to this effect.
在遗传性肥胖小鼠obob中发现了多种行为和神经化学异常，包括食欲亢进、下丘脑去甲肾上腺素（NE）水平升高以及α-1受体密度增加。肥胖突变体对神经药理学药物的反应也异常。在当前研究中，给食物受限（6小时进食时间）的obob小鼠和瘦小鼠施用了α-2受体阻滞剂育亨宾和萝芙木碱。育亨宾和萝芙木碱显著降低了obob小鼠和瘦小鼠3小时和6小时的食物摄入量。然而，obob小鼠比瘦小鼠对这种厌食作用更敏感。有效剂量的育亨宾对缺水的瘦小鼠的饮水量没有影响，表明该药物对食物摄入有特定作用。低剂量（50和100微克）的α-2激动剂可乐定增加了obob小鼠1小时的食物摄入量，但对瘦小鼠的食物摄入量没有影响。obob小鼠和瘦小鼠在下丘脑中α-受体的数量上没有差异。结果表明，通过操纵α-2受体来改变NE释放可以改变食物摄入量，并且obob突变体对这种作用特别敏感。
