Chaouloff F, Coupry I, Baudrie V
Laboratoire de Pharmacologie, CNRS, CHUNecker, Paris, France.
Pharmacol Biochem Behav. 1995 Feb;50(2):309-12. doi: 10.1016/0091-3057(94)00297-v.
Past studies have indicated that genetically obese Zucker (fa/fa) rats are hypercorticoid, and that this neuroendocrine alteration plays a key role in the syndrome. In keeping with the proposal that glucocorticoids may upregulate central 5-HT2A receptors, we have studied the effects of acute and repeated 5-HT2A receptor stimulation by 1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane (DOI) in lean and obese Zucker rats. Acute injection of DOI (2 mg/kg, SC) elicited a lower number of head shakes in obese rats compared to that measured in lean rats. Conversely, neither DOI-elicited decreases in food intakes and body weights nor cortical [3H]ketanserin binding were affected by obesity. In rats repeatedly pretreated with DOI, biochemical and functional indices of 5-HT2A receptor downregulation failed to reveal an effect of obesity. It is suggested that 5-HT2A receptor-mediated functions, but not their downregulation, may be differentially affected in the hypercorticoid obese Zucker rat.
过去的研究表明，遗传性肥胖的 Zucker（fa/fa）大鼠存在高皮质醇现象，且这种神经内分泌改变在该综合征中起关键作用。鉴于糖皮质激素可能上调中枢 5 - HT2A 受体这一观点，我们研究了 1 -（4 - 碘 - 2,5 - 二甲氧基苯基）- 2 - 氨基丙烷（DOI）对正常和肥胖 Zucker 大鼠急性及反复刺激 5 - HT2A 受体的影响。与正常大鼠相比，急性注射 DOI（2 mg/kg，皮下注射）引起肥胖大鼠的甩头次数减少。相反，DOI 引起的食物摄入量和体重下降以及皮质[3H]酮色林结合不受肥胖影响。在用 DOI 反复预处理的大鼠中，5 - HT2A 受体下调的生化和功能指标未显示出肥胖的影响。提示在高皮质醇的肥胖 Zucker 大鼠中，5 - HT2A 受体介导的功能可能受到不同影响，但其下调不受影响。
