Bellinger Larry L, Wellman Paul J, Cepeda-Benito Antonio, Kramer Phillip R, Guan Guoqiang, Tillberg Connie M, Gillaspie Priscilla R, Hill E Gerald
Department of Biomedical Sciences, Baylor College of Dentistry, 3302 Gaston Avenue, Dallas, TX 75246, USA.
Pharmacol Biochem Behav. 2005 Mar;80(3):437-44. doi: 10.1016/j.pbb.2004.12.010.
Previously we observed in male rats that intermittent administration of nicotine (NIC) during the dark phase reduces food intake (FI) by initially decreasing only dark phase meal size. This was followed several days later by an increase in dark phase meal frequency such that FI returned to normal, while body weight remained suppressed. Termination of NIC treatment resulted in a modest dark phase hyperphagia. Since some human females use NIC as a weight control drug, the present study investigated changes in FI and body weight regulation in adult female rats treated for five estrous cycles with saline or a 1.40 mg/kg/day (free base) dose of NIC, which was given in four equal i.p. doses during the dark phase. The rats were followed for 15 days after cessation of NIC. Initially both dark and light phase FI were reduced and this was caused by an immediate decrease in dark and light phase meal size; the attenuation of meal size continued after cessation of NIC. On day 7 of NIC, the rats compensated by significantly increasing the number of dark, but not light, phase meals they took. This resulted in a normal 24-h FI, which was caused by a dark phase increase in FI coupled with a continued decrease in light phase FI. Importantly, these changes in meal patterns persisted for some time after termination of NIC. Upon NIC cessation, the NIC group showed no hyperphagia even though their body weight was significantly decreased. These results document that administration of NIC during the dark phase resulted in a reorganization of the microstructure of FI in females rats that resembles, but does not exactly duplicate, that observed in male rats. Like males, long lasting alterations in the microstructure of FI (e.g., meal size and meal number), were noted in female rats for up to 2 weeks after cessation of NIC. These results differ from studies in which NIC was given continuously 24-h per day and indicate that dark phase NIC administration in rats may represent an appropriate model to study the impact of NIC on meal patterns.
此前我们在雄性大鼠中观察到，在黑暗期间歇性给予尼古丁（NIC），最初仅通过减少黑暗期的餐量来降低食物摄入量（FI）。几天后，黑暗期的进餐频率增加，使得食物摄入量恢复正常，而体重仍受到抑制。停止尼古丁治疗会导致黑暗期适度的食欲亢进。由于一些成年女性将尼古丁用作控制体重的药物，本研究调查了成年雌性大鼠在五个动情周期中用生理盐水或1.40毫克/千克/天（游离碱）剂量的尼古丁进行治疗后的食物摄入量和体重调节变化，该剂量在黑暗期分四次等量腹腔注射。在停止尼古丁治疗后，对大鼠进行了15天的跟踪观察。最初，黑暗期和光照期的食物摄入量均减少，这是由于黑暗期和光照期的餐量立即减少所致；停止尼古丁治疗后，餐量的减少仍在持续。在尼古丁治疗的第7天，大鼠通过显著增加黑暗期（而非光照期）的进餐次数来进行代偿。这导致了正常的24小时食物摄入量，这是由于黑暗期食物摄入量增加以及光照期食物摄入量持续减少所致。重要的是，这些进餐模式的变化在停止尼古丁治疗后的一段时间内仍然存在。停止尼古丁治疗后，尼古丁组即使体重显著下降，也没有出现食欲亢进。这些结果表明，在黑暗期给予尼古丁会导致雌性大鼠食物摄入微观结构的重新组织，这种情况与雄性大鼠中观察到的相似，但并不完全相同。与雄性大鼠一样，在停止尼古丁治疗后的长达2周时间内，雌性大鼠的食物摄入微观结构（如餐量和进餐次数）出现了长期变化。这些结果与每天24小时持续给予尼古丁的研究不同，表明在大鼠黑暗期给予尼古丁可能是研究尼古丁对进餐模式影响的合适模型。
