Department of Psychology, Leeds Metropolitan University, D420 Civic Quarter, Calverley Street, Leeds, LS1 3HE, UK.
Psychopharmacology (Berl). 2011 Oct;217(4):455-73. doi: 10.1007/s00213-011-2296-2. Epub 2011 Apr 19.
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.
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.
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.
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.
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.
重度吸烟者表现出比不吸烟者更高水平的冲动选择和行为抑制。然而，迄今为止，尼古丁使用与不同冲动维度之间的关系尚未得到系统评估。
设计了一系列研究来评估尼古丁和烟碱受体拮抗剂美加明单独以及与尼古丁联合使用对大鼠冲动选择和行为抑制的急性剂量反应效应。
分别训练几组大鼠进行对称强化的 Go/No-Go 任务，以测量抑制水平；并进行系统的延迟奖励任务，以测量冲动选择水平。在每个任务中，一旦训练完成，所有动物都接受急性治疗，给予尼古丁（0.125、0.25、0.5 和 1.0 mg/kg）、美加明（0.1、0.3 和 1.0 mg/kg）和不同剂量的美加明（0.1、0.3 和 1.0 mg/kg），然后给予尼古丁（0.5 mg/kg）。此外，还进行了一项实验，评估了初级动机（预饱食和禁食）变化对这两个任务中表现的影响。
急性尼古丁增加了冲动选择和行为抑制，这些作用被美加明预处理所阻断。美加明单独给药不会改变冲动行为。预饱食对行为测量的影响，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作用。
目前的发现支持这样一种假设，即吸烟者的冲动性增加可能部分是尼古丁的直接急性作用的结果。因此，药物诱导的冲动性变化可能在向尼古丁依赖的过渡和维持中发挥关键作用。
