Finger Beate C, Dinan Timothy G, Cryan John F
School of Pharmacy, Food for Health Ireland, University College Cork, Cork, Ireland.
Behav Pharmacol. 2011 Oct;22(7):624-32. doi: 10.1097/FBP.0b013e32834afee6.
Behavioral satiety sequence (BSS) is a useful paradigm to assess the effects of orexigenic and anorexigenic profiles of novel pharmacological and genetic manipulations in rodents. To date, no studies have described the satiety profile of leptin-deficient ob/ob mice, an important animal model of obesity in this task. Furthermore, no studies have described changes in the BSS after treatment with ghrelin receptor ligands, which have become an attractive therapeutic target in obesity drug discovery efforts. BSS testing was carried out in ob/ob mice and their lean controls. After baseline analysis, effects of ghrelin (2 nmol/10 g) and of the ghrelin receptor antagonist (D-Lys)-GHRP-6 (66.6 and 133.3 nmol/10 g) were studied in BSS in mice of both genotypes. The baseline BSS profile of ob/ob mice showed an increased eating and a decreased resting activity. Ob/ob mice presented with a decreased sensitivity to the stimulation with ghrelin and with the ghrelin receptor antagonist, which caused strong anorexic and adverse side effects in lean mice, thereby disrupting the BSS profile. BSS is an indispensable tool for parsing the role of the ghrelinergic system in satiety, to characterize transgenic mice and to elicit behavioral feeding profiles of novel anorectic agents.
行为性饱足序列（BSS）是一种用于评估新型药理学和基因操作的促食欲和抑食欲特性对啮齿动物影响的有用范式。迄今为止，尚无研究描述瘦素缺乏的ob/ob小鼠（肥胖症的一种重要动物模型）在此任务中的饱足特性。此外，也没有研究描述用胃饥饿素受体配体治疗后BSS的变化，胃饥饿素受体配体已成为肥胖症药物研发中一个有吸引力的治疗靶点。在ob/ob小鼠及其瘦型对照中进行了BSS测试。在基线分析后，研究了胃饥饿素（2 nmol/10 g）和胃饥饿素受体拮抗剂（D-Lys）-GHRP-6（66.6和133.3 nmol/10 g）对两种基因型小鼠BSS的影响。ob/ob小鼠的基线BSS特性显示进食增加而静息活动减少。ob/ob小鼠对胃饥饿素和胃饥饿素受体拮抗剂的刺激敏感性降低，胃饥饿素和胃饥饿素受体拮抗剂在瘦型小鼠中会引起强烈的厌食和不良副作用，从而扰乱BSS特性。BSS是剖析胃饥饿素能系统在饱足中的作用、表征转基因小鼠以及引出新型厌食剂行为性进食特性的不可或缺的工具。
