Currie P J, Wilson L M
Section of Biopsychology, Clarke Institute of Psychiatry, Toronto, Ontario, Canada.
Pharmacol Biochem Behav. 1992 Dec;43(4):1039-46. doi: 10.1016/0091-3057(92)90478-x.
Biochemical abnormalities in the hypothalamus of the genetically obese (C57B1/6J, ob/ob) mouse, including increased levels of endogenous norepinephrine (NE) in the paraventricular nucleus (PVN) and reduced medial hypothalamic NE metabolism, have been cited as evidence of a CNS defect contributing to altered caloric intake in this genetic strain. In the current study, the alpha 2-antagonist yohimbine (YOH) and the alpha 2-agonist clonidine (CLON) were administered systemically to 6-h meal-feeding obese and lean mice. Yohimbine (3-5 mg/kg, IP) significantly reduced total energy intake and intake of carbohydrate and fat, in both phenotypes, without altering protein intake. In contrast, CLON (25 micrograms/kg, IP) potentiated feeding, resulting in a shift in macronutrient selection toward a significant increase in the proportional intake of carbohydrate. Obese mice, however, showed an enhanced behavioral response to CLON injection. Pretreatment with 1 mg/kg YOH, a dose that alone did not significantly alter energy intake or diet selection, blocked CLON's stimulatory effect on feeding and carbohydrate preference. These results are consistent with a role for alpha 2-noradrenergic receptors in appetite regulation of ob/ob and lean mice and suggest that disturbances in this system may be involved in the development of genetic obesity.
遗传性肥胖（C57B1/6J，ob/ob）小鼠下丘脑的生化异常，包括室旁核（PVN）中内源性去甲肾上腺素（NE）水平升高以及下丘脑内侧NE代谢降低，已被视为中枢神经系统缺陷的证据，这种缺陷导致了该遗传品系热量摄入的改变。在本研究中，对限时6小时进食的肥胖和瘦小鼠全身给予α2拮抗剂育亨宾（YOH）和α2激动剂可乐定（CLON）。育亨宾（3 - 5毫克/千克，腹腔注射）显著降低了两种表型小鼠的总能量摄入以及碳水化合物和脂肪的摄入量，而蛋白质摄入量未改变。相比之下，可乐定（25微克/千克，腹腔注射）增强了进食，导致大量营养素选择发生变化，碳水化合物的比例摄入量显著增加。然而，肥胖小鼠对可乐定注射表现出增强的行为反应。用1毫克/千克育亨宾预处理，该剂量单独使用时不会显著改变能量摄入或饮食选择，可阻断可乐定对进食和碳水化合物偏好的刺激作用。这些结果与α2 - 去甲肾上腺素能受体在ob/ob和瘦小鼠食欲调节中的作用一致，并表明该系统的紊乱可能与遗传性肥胖的发生有关。
