Acute nicotine increases both impulsive choice and behavioural disinhibition in rats
Acute nicotine increases both impulsive choice and behavioural disinhibition in rats
复制标题
DOI：
10.1007/s00213-011-2296-2
复制
发表时间：
2011-10-01
影响因子：
3.4
通讯作者：
Harrison, Amanda A.
中科院分区：
文献类型：
--
作者：
Kolokotroni, Katerina Zoe;Rodgers, Robert J.;Harrison, Amanda A.
理论基础重度吸烟者比不吸烟者表现出更多的冲动选择和行为去抑制。然而，到目前为止，尼古丁的使用与不同的冲动性维度之间的关系还没有得到系统的评估。目的一系列研究旨在评估尼古丁和尼古丁受体拮抗剂Mecamylamine单独以及与尼古丁联合使用对大鼠冲动选择和行为去抑制的急性剂量-反应效应。方法对不同组的大鼠进行对称强化的去抑制/不去去任务训练，以测量去抑制水平和系统延迟奖励任务，以测量冲动选择水平。训练完成后，每个任务中的所有动物都在尼古丁(0.125.5、0.2 5、0.5和1.0 mg/kg)、甲氨基甲胺(0.1、0.3和1.0 mg/kg)和不同剂量的甲氨基甲胺(0.1、0.3和1.0 mg/kg)和尼古丁(0.5 mg/kg)之前进行急性处理。另一项实验评估了基本动机(压力和禁食)的变化对这两项任务的表现的影响。结果急性尼古丁增加了冲动选择和行为去抑制，这一效应可被甲氨基甲胺预先处理所阻断。单独使用甲基戊胺并不能改变冲动行为。压力对表现测量的影响的缺乏表明，观察到的尼古丁诱导的冲动不能归因于化合物的厌食活性。结论目前的发现支持这样的假设，即吸烟者的冲动增强可能部分是尼古丁的直接急性影响的结果。因此，药物诱导的冲动变化可能在尼古丁依赖的转变和维持中发挥关键作用。
Rationale Heavy smokers exhibit greater levels of impulsive choice and behavioural disinhibition than non-smokers. To date, however, the relationship between nicotine use and differing dimensions of impulsivity has not been systematically assessed.Objectives A series of studies was designed to assess the acute dose-response effects of nicotine and the nicotinic receptor antagonist mecamylamine alone, and in combination with nicotine, on impulsive choice and behavioural disinhibition in rats.Methods Separate groups of rats were trained on a symmetrically reinforced go/no-go task to measure levels of disinhibition and a systematic delayed reward task to measure levels of impulsive choice. Once trained, all animals in each task were treated acutely with nicotine (0.125, 0.25, 0.5 and 1.0 mg/kg), mecamylamine (0.1, 0.3 and 1.0 mg/kg) and varying doses of mecamylamine (0.1, 0.3 and 1.0 mg/kg) prior to nicotine (0.5 mg/kg). An additional experiment assessed the effects of alterations in primary motivation (presatiation and fasting) on performance in both tasks.Results Acute nicotine increased both impulsive choice and behavioural disinhibition, effects that were blocked by pre-treatment with mecamylamine. Mecamylamine when administered alone did not alter impulsive behaviour. The lack of effect of presatiation on performance measures suggests that the observed nicotine-induced impulsivity cannot be attributed to the anorectic activity of the compound.Conclusions Present findings support the hypothesis that heightened impulsivity in smokers may in part be a consequence of the direct acute effects of nicotine. As such, drug-induced changes in impulsivity may play a critical role in the transition to and maintenance of nicotine dependence.