Grignaschi G, Fanelli E, Scagnol I, Samanin R
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Br J Pharmacol. 1999 Jul;127(5):1190-4. doi: 10.1038/sj.bjp.0702633.
The effect of the 5-hydroxytryptamine (5-HT) and noradrenaline (NA) reuptake inhibitor sibutramine was studied in food deprived, neuropeptide Y (NPY)- or muscimol-injected rats. Sibutramine dose-dependently reduced feeding caused by food-deprivation (ED50 = 5.1+/-0.8 mg kg(-1)) or by NPY injection into the paraventricular nucleus of the hypothalamus (ED50 = 6.0+/-0.5 mg kg(-1)). The increase in food intake caused by muscimol injected into the dorsal raphe was not modified by sibutramine (1-10 mg kg(-1)). The hypophagic effect of 5.1 mg kg(-1) sibutramine in food-deprived rats was studied in rats pretreated with different serotonin receptor antagonists. Metergoline (non-selective, 0.3 and 1.0 mg kg(-1)), ritanserin (5-HT2A/2C, 0.5 and 1.0 mg kg(-1)) and GR127935 (5-HT1B/1D), 0.5 and 1.0 mg kg(-1)) did not modify the hypophagic effect of sibutramine, while SB206553 (5-HT2B/2C, 5 and 10 mg kg(-1)) slightly but significantly reduced it (Fint(2.53) = 3.4; P<0.05). The reduction in food intake caused by 6.0 mg kg(-1) sibutramine in NPY-injected rats was not modified by GR127935 (1.0 mg kg(-1)). The results suggest that, with the possible exception of a partial involvement of 5-HT2B/2C receptors in sibutramine's hypophagia in food-deprived rats, 5-HT1 and 5-HT2 receptor subtypes do not play an important role in the hypophagic effect of sibutramine, at least in the first 2 h after injection.
在食物剥夺、注射神经肽Y（NPY）或蝇蕈醇的大鼠中研究了5-羟色胺（5-HT）和去甲肾上腺素（NA）再摄取抑制剂西布曲明的作用。西布曲明剂量依赖性地减少由食物剥夺（半数有效剂量[ED50]=5.1±0.8毫克/千克）或向下丘脑室旁核注射NPY（ED50=6.0±0.5毫克/千克）引起的进食。向中缝背核注射蝇蕈醇引起的食物摄入量增加未被西布曲明（1-10毫克/千克）改变。在预先用不同5-羟色胺受体拮抗剂处理的大鼠中研究了5.1毫克/千克西布曲明对食物剥夺大鼠的摄食减少作用。麦角新碱（非选择性，0.3和1.0毫克/千克）、利坦色林（5-HT2A/2C，0.5和1.0毫克/千克）和GR127935（5-HT1B/1D，0.5和1.0毫克/千克）未改变西布曲明的摄食减少作用，而SB206553（5-HT2B/2C，5和10毫克/千克）轻微但显著地降低了该作用（Fint(2.53)=3.4；P<0.05）。GR127935（1.0毫克/千克）未改变6.0毫克/千克西布曲明对注射NPY大鼠进食的减少作用。结果表明，除了5-HT2B/2C受体可能部分参与西布曲明对食物剥夺大鼠的摄食减少作用外，5-HT1和5-HT2受体亚型在西布曲明的摄食减少作用中至少在注射后的前2小时不发挥重要作用。
