Evidence that mesoaccumbens dopamine and locomotor responses to nicotine in the rat are influenced by pretreatment dose and strain
Evidence that mesoaccumbens dopamine and locomotor responses to nicotine in the rat are influenced by pretreatment dose and strain
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DOI：
10.1007/s002130100852
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发表时间：
2001-10-01
影响因子：
3.4
通讯作者：
Balfour, DJK
中科院分区：
文献类型：
--
作者：
Iyaniwura, TT;Wright, AE;Balfour, DJK
理论基础：中伏隔脑多巴胺对尼古丁的敏感反应与尼古丁依赖的发展有关。这项研究探索了在两种不同基线活动水平的大鼠中引起反应的尼古丁剂量。方法：雄性Sprague-Dawley和Lister大鼠每天皮下注射(-)-尼古丁，剂量范围为0.03 mg/kg ~ 0.90 mg/kg，连续7天。第9天，将有意识自由活动的大鼠置于活动箱中，给予0.4 mg/kg尼古丁刺激，进行微透析研究。结果：初给药大鼠急性给予尼古丁刺激伏隔壳多巴胺溢出，而非核多巴胺溢出。经尼古丁预处理（0.03 mg/kg/d和0.10 mg/kg/d）的Sprague-Dawley大鼠显示伏隔核多巴胺基础溢出增加。0.10 mg/kg/day或0.30 mg/kg/day的预处理，而不是0.03 mg/kg/day或0.90 mg/kg/day，也会在测试当天引起对尼古丁刺激的致敏反应。运动反应对尼古丁的致敏表现出简单的剂量-反应关系，在0.90 mg/kg/天预处理的动物中观察到最大的致敏。在李斯特，戴着帽子的老鼠。尼古丁预处理减少了伏隔核的基础多巴胺溢出，并且没有引起对尼古丁后续挑战的致敏。结论：脑伏隔核多巴胺对尼古丁的致敏反应受预处理剂量和所用大鼠品系的影响。它与药物致敏运动反应的表达没有直接关系，因此，可能与药物的其他精神药理学特性有关，包括依赖性。
Rationale: Sensitisation of the mesoaccumbens dopamine response to nicotine has been implicated in the development of nicotine dependence. This study explored the doses of nicotine that elicit the response in two strains of rats that differ in their baseline levels of activity. Methods: Male Sprague-Dawley and Lister hooded rats were pretreated with daily subcutaneous injections of (-)-nicotine for 7 days at doses ranging from 0.03 mg/kg to 0.90 mg/kg. Microdialysis studies were performed on day 9 in conscious freely moving rats, placed in an activity box and challenged with 0.4 mg/kg nicotine. Results: The acute administration of nicotine to drug-naive rats stimulated dopamine overflow in the accumbal shell but not the core. Sprague-Dawley rats, pretreated with nicotine (0.03 mg/kg/day and 0.10 mg/kg/day) showed increased basal overflow of dopamine in the accumbal core. Pretreatment with 0.10 mg/kg/day or 0.30 mg/kg/day, but not 0.03 mg/kg/day or 0.90 mg/kg/day, also caused sensitisation of the response to a nicotine challenge on the test day. Sensitisation of the locomotor response to nicotine exhibited a simple dose-response relationship, with the largest sensitisation being observed in animals pretreated with 0.90 mg/kg/day. In Lister hooded rats. pretreatment with nicotine reduced basal dopamine overflow in the accumbal core and did not cause sensitisation to a subsequent challenge with nicotine. Conclusions: Sensitisation of the mesoaccumbens dopamine response to nicotine is influenced by pretreatment dose and the strain of rats used. It is not related directly to the expression of sensitised locomotor responses to the drug and, therefore, may be implicated in other psychopharmacological properties of the drug, including dependence.