Ishii Y, Blundell J E, Halford J C G, Upton N, Porter R, Johns A, Rodgers R J
Behavioural Pharmacology Laboratory, School of Psychology, University of Leeds, Leeds LS2 9JT, UK.
Physiol Behav. 2004 Mar;81(1):129-40. doi: 10.1016/j.physbeh.2004.01.009.
Recent studies have shown that acute systemic administration of the selective orexin-1 receptor antagonist SB-334867 significantly reduces food intake in rats. Although this anorectic action of orexin-1 receptor blockade is associated with an acceleration in the transition from eating to resting, it is widely recognised that the behavioural indices of satiety are not dissimilar to those of illness. In this context, Experiment 1 confirmed a significant anorectic effect of 90 (but not 60) mg/kg lithium chloride (LiCl) in male rats presented with palatable mash in the home-cage environment. Experiment 2 employed a continuous monitoring technique to contrast the effects of LiCl (90 mg/kg) and SB-334867 (10 and 30 mg/kg) on food intake and behaviour during a 1-h test with palatable mash. SB-334867 dose-dependently inhibited food intake, with the higher dose producing a comparable degree of appetite suppression (approximately 40%) to that seen with LiCl. Despite equivalent anorectic action, the two compounds produced very different effects on behaviour. LiCl reduced active behaviours (locomotion, rearing, grooming and sniffing), slowed the rate of eating and disrupted the behavioural satiety sequence (BSS). In contrast, SB-334867 (30 mg/kg) decreased the duration of feeding and grooming, and modestly accelerated the transition between eating and resting. Furthermore, whereas LiCl failed to alter posttreatment bodyweight gain, SB-334867 (30 mg/kg) produced a significant weight loss in the 24-h period immediately following injection. Overall, the divergent profiles obtained with equianorectic doses of LiCl and SB-334867 provide convincing evidence for the behavioural selectivity of SB-334867-induced anorexia.
最近的研究表明，急性全身给予选择性食欲素-1受体拮抗剂SB-334867可显著减少大鼠的食物摄入量。尽管食欲素-1受体阻断的这种厌食作用与进食到休息转变的加速有关，但人们普遍认识到饱腹感的行为指标与疾病的指标并无不同。在此背景下，实验1证实，在笼养环境中给雄性大鼠投喂美味软食时，90（而非60）mg/kg的氯化锂（LiCl）具有显著的厌食作用。实验2采用连续监测技术，对比LiCl（90 mg/kg）和SB-334867（10和30 mg/kg）在1小时美味软食测试期间对食物摄入量和行为的影响。SB-334867剂量依赖性地抑制食物摄入，较高剂量产生的食欲抑制程度（约40%）与LiCl相当。尽管厌食作用相当，但这两种化合物对行为产生了非常不同的影响。LiCl减少了主动行为（运动、竖毛、梳理和嗅探），减缓了进食速度并打乱了行为饱腹感序列（BSS）。相比之下，SB-334867（30 mg/kg）减少了进食和梳理的持续时间，并适度加速了进食和休息之间的转变。此外，LiCl未能改变治疗后的体重增加，而SB-334867（30 mg/kg）在注射后的24小时内导致显著体重减轻。总体而言，等厌食剂量的LiCl和SB-334867所获得的不同结果为SB-334867诱导的厌食症的行为选择性提供了令人信服的证据。
