Once weekly administration of nicotine produces long-lasting locomotor sensitization in rats via a nicotinic receptor-mediated mechanism
Once weekly administration of nicotine produces long-lasting locomotor sensitization in rats via a nicotinic receptor-mediated mechanism
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DOI：
10.1007/s002130100747
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发表时间：
2001-08-01
影响因子：
3.4
通讯作者：
Dwoskin, LP
中科院分区：
文献类型：
--
作者：
Miller, DK;Wilkins, LH;Dwoskin, LP
基本原理：慢性尼古丁给药导致神经元功能的动态变化，表现为动物的行为敏化和吸烟者的成瘾。目的：本研究旨在确定每周一次尼古丁注射是否会因尼古丁受体激活而对尼古丁的运动激活特性产生致敏作用。方法：每周一次，连续6周，大鼠（s.c.）两次盐水注射或盐水和尼古丁（0.35mg/kg），并监测自发活动。将大鼠留在饲养笼中21天，随后注射适当的治疗药物，以确定致敏作用是否持续。大鼠也注射生理盐水或美加明（1.2 mg/kg），然后每周注射一次生理盐水或尼古丁，持续6周，以确定美加明的作用以及是否抑制尼古丁诱导的多动症。另一组每周注射一次生理盐水和尼古丁，持续4周;第5周，给予美加明和尼古丁，以确定美加明是否抑制敏化的表达。单独的组每周注射一次美加明和尼古丁，持续5周或6周;在第6周或第9周，分别注射生理盐水和尼古丁，以确定美加明是否抑制致敏反应的启动。结果如下：在28天内注射4次尼古丁后，对尼古丁的运动激活特性产生了致敏作用，并在无药物治疗21天后持续存在。美加明没有改变活性，但减弱了敏化的起始和表达。结论：每周一次尼古丁给药后的尼古丁受体激活产生持久的行为敏化，表明即使是不频繁的尼古丁暴露也会启动与尼古丁成瘾相关的神经适应性过程。
Rationale: Chronic nicotine administration results in dynamic changes in neuronal function, expressed as behavioral sensitization in animals and addiction in smokers. Objectives: The present study was undertaken to determine whether once-weekly nicotine injection produces sensitization to the locomotor-activating properties of nicotine as a result of nicotinic receptor activation. Methods: Once weekly for 6 weeks, rats were administered (s.c.) two saline injections or saline and nicotine (0.35 mg/kg), and locomotor activity was monitored. Rats remained in the home cage for 21 days, and subsequently were injected with the appropriate treatment to determine whether sensitization persisted. Rats were also injected with saline or mecamylamine (1.2 mg/kg) followed by saline or nicotine once weekly for 6 weeks to determine the effect of mecamylamine and whether it inhibited nicotine-induced hyperactivity. A separate group was injected with saline and nicotine once weekly for 4 weeks; on week 5, mecamylamine and nicotine were administered to determine whether mecamylamine inhibited the expression of sensitization. Separate groups were injected with mecamylamine and nicotine once weekly for 5 weeks or 6 weeks; on week 6 or week 9, respectively, saline and nicotine were injected to determine whether mecamylamine inhibited the initiation of sensitization. Results: Sensitization to the locomotor-activating properties of nicotine developed following four nicotine injections across a 28-day period and persisted following 21 days of no drug treatment. Mecamylamine did not alter activity but attenuated both the initiation and expression of sensitization. Conclusions: Nicotinic receptor activation following once-weekly nicotine administration produces long-lasting behavioral sensitization, suggesting that even infrequent nicotine exposure initiates neuroadaptive processes associated with nicotine addiction.