Mazur Gabriel J, Wood-Isenberg Gabriel, Watterson Elizabeth, Sanabria Federico
Department of Psychology, Arizona State University, PO Box 871104, Tempe, AZ, 85287-1104, USA.
Psychopharmacology (Berl). 2014 Jun;231(12):2471-82. doi: 10.1007/s00213-013-3412-2. Epub 2014 Jan 11.
Attention-deficit hyperactivity disorder (ADHD) is associated with a higher prevalence of smoking, which may be related to potential therapeutic effects of nicotine on ADHD symptoms. Whereas nicotine offers robust improvements in sustained attention, the effects of nicotine on impulsivity are unclear.
The present study examined the effects of nicotine on the response inhibition capacity of spontaneously hypertensive rats (SHR), an animal model of ADHD, compared to that of a normotensive control Wistar Kyoto (WKY), using the fixed minimum interval (FMI) schedule of reinforcement.
Tests were conducted following acute injections of subcutaneous nicotine (0.1-0.6 mg/kg). On each FMI trial, the first lever press initiated an inter-response time (IRT); a head entry into a food receptacle terminated the IRT. IRTs longer than 6 s were intermittently reinforced with sucrose.
A model that assumes that only a proportion of IRTs are sensitive to the timing contingencies of the FMI provided a close fit to the data, regardless of strain or treatment. No baseline difference in FMI performance was observed between SHR and WKY. Nicotine reduced the duration of timed IRTs and the duration of latencies to the IRT-initiating lever press similarly for both strains. Nicotine dose-dependently increased the proportion of timed IRTs; the dose-response curve was shifted leftwards in SHR relative to WKY.
These results suggest that nicotine (a) reduces response-inhibition capacity, (b) enhances the reinforcing efficacy of sucrose, and (c) dose-dependently enhances attention-like sensitivity to contingencies of reinforcement, through mechanisms that are yet unknown.
注意力缺陷多动障碍(ADHD)与较高的吸烟率相关,这可能与尼古丁对ADHD症状的潜在治疗作用有关。虽然尼古丁能显著改善持续注意力,但尼古丁对冲动性的影响尚不清楚。
本研究使用固定最小间隔(FMI)强化程序,比较尼古丁对自发性高血压大鼠(SHR,一种ADHD动物模型)与正常血压对照Wistar Kyoto大鼠(WKY)反应抑制能力的影响。
在皮下注射急性尼古丁(0.1 - 0.6毫克/千克)后进行测试。在每个FMI试验中,第一次按压杠杆启动反应间隔时间(IRT);头部进入食物容器则终止IRT。超过6秒的IRT会间歇性地用蔗糖强化。
一个假设只有一部分IRT对FMI的时间意外情况敏感的模型与数据拟合良好,无论品系或处理如何。SHR和WKY之间在FMI表现上未观察到基线差异。尼古丁对两种品系的定时IRT持续时间和IRT启动杠杆按压的延迟持续时间的减少作用相似。尼古丁剂量依赖性地增加了定时IRT的比例;相对于WKY,SHR的剂量 - 反应曲线向左移动。
这些结果表明,尼古丁(a)降低反应抑制能力,(b)增强蔗糖的强化效果,以及(c)通过尚不清楚的机制剂量依赖性地增强对强化意外情况的注意力样敏感性。