Collins A C, Romm E, Wehner J M
Institute for Behavioral Genetics, University of Colorado, Boulder 80309.
Brain Res Bull. 1990 Sep;25(3):373-9. doi: 10.1016/0361-9230(90)90222-l.
Saline or nicotine (0.8 mg/kg/hr) was administered chronically to rats via subcutaneous infusion for 7 days. After chronic treatment, the effects of a challenge dose of nicotine, injected subcutaneously, on open-field activity and body temperature were measured. Nicotine responses were measured 2 hours after infusion had been stopped (day 0) or 1, 2, 4, 8, or 21 days after cessation of treatment. Brain nicotinic receptors were measured using nicotine binding or bungarotoxin binding in six brain regions. Tolerance to nicotine's effects on open-field activity and body temperature were observed; this tolerance was lost before the fourth day of withdrawal. Both nicotine and BTX binding were increased after chronic nicotine treatment. The return of the receptors to control values was dependent on brain region, but in general receptors were still increased at 4 days after withdrawal. The half-lives for receptors returning to normal were greater for nicotine binding compared to BTX binding. These results suggest that a relatively short-lived tolerance results from chronic nicotine infusion and that alterations in nicotinic receptors can be dissociated from behavioral tolerance.
通过皮下输注对大鼠进行为期7天的慢性生理盐水或尼古丁（0.8毫克/千克/小时）给药。慢性治疗后，测量皮下注射挑战剂量尼古丁对旷场活动和体温的影响。在输注停止后2小时（第0天）或停止治疗后1、2、4、8或21天测量尼古丁反应。使用尼古丁结合或银环蛇毒素结合在六个脑区测量脑烟碱受体。观察到对尼古丁对旷场活动和体温影响的耐受性；这种耐受性在戒断的第四天之前消失。慢性尼古丁治疗后，尼古丁和银环蛇毒素结合均增加。受体恢复到对照值取决于脑区，但一般来说，戒断后4天受体仍增加。与银环蛇毒素结合相比，尼古丁结合的受体恢复正常的半衰期更长。这些结果表明，慢性尼古丁输注会导致相对短暂的耐受性，并且烟碱受体的改变可以与行为耐受性分离。
