Thorsell A, Caberlotto L, Rimondini R, Heilig M
NEUROTEC, Karolinska Institutet, SE-141 86, Stockholm, Sweden.
Pharmacol Biochem Behav. 2002 Mar;71(3):425-30. doi: 10.1016/s0091-3057(01)00678-5.
Leptin decreases food intake through actions in the hypothalamus, partly through interactions with neuropeptide Y (NPY). However, NPY also produces behavioral antistress effects mediated inter alia through the amygdala. If leptin generally suppresses NPY function, the utility of leptin-mimics for treatment of obesity might be limited. Here, we therefore compared the effects of intracerebroventricular leptin on hypothalamic and amygdala NPY expression, as well as the respective related behaviors, i.e., feeding and experimental anxiety. Rats were injected intracerebroventricularly with leptin once daily for 6 days. Leptin-treated subjects consumed significantly less chow and had reduced body weight at the end of the treatment period compared to saline-treated controls. This was accompanied by a significant suppression of hypothalamic NPY expression. In contrast, the expression of NPY within the amygdala was unaffected by leptin. In parallel, in an established animal model of anxiety, the elevated plus-maze, no effect of leptin on anxiety-related behaviors was observed. In conclusion, leptin selectively affects the hypothalamic NPY system and its functional outflow, i.e., feeding and endocrine stress responses. Despite modifying endocrine responses, leptin treatment does not affect behavioral measures of experimental anxiety.
瘦素通过在下丘脑发挥作用来减少食物摄入，部分是通过与神经肽Y（NPY）相互作用来实现的。然而，NPY还会产生行为抗应激效应，尤其是通过杏仁核介导。如果瘦素普遍抑制NPY功能，那么瘦素模拟物在治疗肥胖症方面的效用可能会受到限制。因此，在此我们比较了脑室内注射瘦素对下丘脑和杏仁核NPY表达的影响，以及各自相关的行为，即进食和实验性焦虑。大鼠每天脑室内注射一次瘦素，持续6天。与生理盐水处理的对照组相比，瘦素处理的大鼠在治疗期结束时摄入的食物显著减少，体重也有所减轻。这伴随着下丘脑NPY表达的显著抑制。相反，杏仁核内NPY的表达不受瘦素影响。同时，在一个既定的焦虑动物模型——高架十字迷宫中，未观察到瘦素对焦虑相关行为有影响。总之，瘦素选择性地影响下丘脑NPY系统及其功能性输出，即进食和内分泌应激反应。尽管瘦素治疗改变了内分泌反应，但并不影响实验性焦虑的行为指标。
