DISSOCIATION OF THE APPARENT RELATIONSHIP BETWEEN NICOTINE TOLERANCE AND UP-REGULATION OF NICOTINIC RECEPTORS
DISSOCIATION OF THE APPARENT RELATIONSHIP BETWEEN NICOTINE TOLERANCE AND UP-REGULATION OF NICOTINIC RECEPTORS
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DOI：
10.1016/0361-9230(90)90222-l
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发表时间：
1990-09-01
影响因子：
3.8
通讯作者：
WEHNER, JM
中科院分区：
文献类型：
--
作者：
COLLINS, AC;ROMM, E;WEHNER, JM
通过皮下输注向大鼠长期施用盐水或尼古丁（0.8 mg/kg/hr）7天。经过长期治疗后，测量了皮下注射的尼古丁攻击剂量对旷场活动和体温的影响。停止输注后 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。使用六个大脑区域的尼古丁结合或银环蛇毒素结合来测量大脑烟碱受体。观察尼古丁对旷场活动和体温的影响的耐受性；这种耐受性在停药第四天之前就消失了。长期尼古丁治疗后，尼古丁和 BTX 结合力均增加。受体恢复到对照值取决于大脑区域，但一般来说，停药后 4 天受体仍然增加。与 BTX 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，长期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能与行为耐受性无关。
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.