Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University Campus, Amravati Road, Nagpur, Maharashtra 440033, India.
Appetite. 2009 Dec;53(3):354-62. doi: 10.1016/j.appet.2009.07.017. Epub 2009 Jul 25.
We investigated the role of corticotropin-releasing factor type 2 (CRF(2)) receptors in acute, chronic and withdrawal effects of nicotine on feeding behavior in rats. Nicotine was injected intraperitoneally, whereas CRF, CRF(2) receptors agonist urocortin-1 or selective antagonist astressin2-B were administered directly into the hypothalamic paraventricular nucleus (PVN). In acute studies, nicotine, CRF or urocortin-1 produced dose dependent anorexia at 2 and 4h post-injection time-points, however, astressin2-B did not alter the food intake. Prior treatment of CRF or urocortin-1 potentiated the anorectic effect of nicotine, while astressin2-B showed opposite response. Chronic administration of nicotine produced tolerance to anorexia and caused persistent weight loss. However, concomitant treatment with CRF or urocortin-1 resulted in early tolerance to nicotine-induced anorexia. In the same set of animals, while CRF pre-treatment potentiated the weight reducing effect of nicotine, urocortin-1 failed to do so. Although abrupt termination of chronic nicotine treatment caused hyperphagia and weight gain, administration of CRF or urocortin-1 prevented these effects. These results suggest that CRF(2) receptors, within the framework of PVN, may contribute to the acute, chronic and withdrawal responses of nicotine on feeding and body weight.
我们研究了促肾上腺皮质释放因子 2 型 (CRF(2)) 受体在尼古丁对大鼠摄食行为的急性、慢性和戒断效应中的作用。尼古丁通过腹腔注射给药，而 CRF、CRF(2) 受体激动剂 urocortin-1 或选择性拮抗剂 astressin2-B 则直接注射到下丘脑室旁核 (PVN)。在急性研究中，尼古丁、CRF 或 urocortin-1 在注射后 2 小时和 4 小时产生剂量依赖性厌食症，但 astressin2-B 并未改变食物摄入量。CRF 或 urocortin-1 的预先处理增强了尼古丁的厌食作用，而 astressin2-B 则表现出相反的反应。慢性给予尼古丁会导致对厌食症的耐受，并导致持续的体重减轻。然而，CRF 或 urocortin-1 的同时给予导致对尼古丁诱导的厌食症的早期耐受。在同一组动物中，虽然 CRF 的预先处理增强了尼古丁的体重减轻作用，但 urocortin-1 却没有。尽管突然停止慢性尼古丁治疗会导致食欲增加和体重增加，但给予 CRF 或 urocortin-1 可预防这些作用。这些结果表明，PVN 内的 CRF(2) 受体可能有助于尼古丁对摄食和体重的急性、慢性和戒断反应。
