Age-dependent effects of the cannabinoid CB1 antagonist SR141716A on food intake, body weight change, and pruritus in rats.
Age-dependent effects of the cannabinoid CB1 antagonist SR141716A on food intake, body weight change, and pruritus in rats.
复制标题
大麻素 CB1 拮抗剂 SR141716A 对大鼠食物摄入、体重变化和瘙痒的年龄依赖性影响。
DOI：
10.1007/s00213-009-1592-6
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发表时间：
2009
影响因子：
3.4
通讯作者：
Walker,EllenA
中科院分区：
文献类型：
--
作者：
Ward,SaraJane;Lefever,TimothyW;Rawls,ScottM;Whiteside,GarthT;Walker,EllenA
基本原理大麻素 CB1 选择性拮抗剂 SR141716A（利莫那班）已被证明可以降低实验动物和人类的体重。此外，SR141716A 可以引起啮齿类动物的抓挠行为，这种行为被假设会导致 SR141716A 诱导的食物摄入量减少。尽管儿童肥胖是一个日益严重的健康问题，但尚不清楚 SR141716A 在调节年轻受试者的食物摄入和其他 CB1 介导的行为方面是否等效。 目的 确定 CB1 受体阻断是否在调节食物和水摄入、体重和抓挠行为方面等效，以及一系列 SR141716A 剂量对产后限食天 (P) 18、28 和对 60 只雄性大鼠进行了研究。测定每个年龄组中 SR141716A 的脑浓度。结果 SR141716A 剂量和年龄依赖性抑制食物和水的摄入以及体重增加并引起抓头，在 P18 和 P28 大鼠中观察到最有效的效果。相对于 P28 和 P60 大鼠，P18 大鼠脑中 SR141716A 浓度显着升高。 SR141716A 引发的抓头行为可被 5-HT2A/2 拮抗剂酮舍林减弱。结论 SR141716A 在调节年幼动物的食物摄入和抓头方面更有效；这些差异可归因于 SR141716A 对 P18 大鼠的脑渗透增加，但对 P28 和 P60 大鼠则不然。此外，SR141716 引起的抓头是通过 5HT 受体拮抗作用调节的，并不是 SR141716A 的厌食作用的影响因素。
RationaleThe cannabinoid CB1 selective antagonist SR141716A (Rimonabant) has been shown to decrease body weight in laboratory animals and humans. Furthermore, SR141716A can elicit scratching behavior in rodents, a behavior that has been hypothesized to contribute to SR141716A-induced decrease in food intake. Although childhood obesity is a rising health issue, it is unknown whether SR141716A is equipotent at modulating food intake and other CB1-mediated behaviors in younger subjects.ObjectiveTo determine whether CB1 receptor blockade is equipotent at modulating food and water intake, body weight, and scratching behavior, the effect of a range of SR141716A doses on these behaviors in food-restricted postnatal day (P) 18, 28, and 60 male rats was investigated. Brain concentrations of SR141716A were determined in each age group.ResultsSR141716A dose- and age-dependently suppressed food and water intake and body weight gain and elicited head scratching, with the most potent effects observed in P18 and P28 rats. Brain concentrations of SR141716A were significantly elevated in P18 rats relative to P28 and P60 rats. SR141716A-elicited head scratching was attenuated by the 5-HT2A/2Cantagonist ketanserin.ConclusionsSR141716A is more potent at modulating food intake and head scratching in very young animals; these differences can be attributed to an increase in brain penetration of SR141716A for P18 but not for P28 and P60 rats. In addition, SR141716-elicited head scratching is modulated by 5HT receptor antagonism and is not a contributing factor to SR141716A's anorectic effects.