Smethells John R, Burroughs Danielle, Saykao Amy, LeSage Mark G
Hennepin Healthcare Research Institute, Minneapolis, MN, United States.
Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, United States.
Front Psychiatry. 2023 May 15;14:1154773. doi: 10.3389/fpsyt.2023.1154773. eCollection 2023.
Attention-deficit/hyperactivity disorder (ADHD) is an independent risk factor for tobacco use disorder. Individuals with ADHD are more likely to begin smoking at a younger age, become a daily smoker sooner, smoke more cigarettes per day, and exhibit greater nicotine dependence than individuals without ADHD. It is unclear whether these findings are due to the reinforcing efficacy of nicotine being greater among individuals with ADHD. The purpose of the present study was to examine this issue using an animal model of ADHD, the spontaneously hypertensive rat (SHR) strain.
Adolescent SHR and Wistar (control) rats were given access to a typically reinforcing nicotine unit dose (30 μg/kg), a threshold reinforcing nicotine dose (4 μg/kg), or saline under an FR 1 (week 1) and FR 2 (week 2) schedule during 23 h sessions to examine acquisition of self-administration. Behavioral economic demand elasticity was then evaluated at the 30 μg/kg dose through an FR escalation procedure.
At the 30 μg/kg dose, SHR rats exhibited a lower average response rate, lower mean active to inactive lever discrimination ratio, and lower proportion of rats acquiring self-administration compared to control rats. During demand assessment, SHR rats showed no significant difference from Wistars in demand intensity (Q) or elasticity (α; i.e., reinforcing efficacy). In addition, no strain difference in acquisition measures were observed at the 4 μg/kg dose.
These findings suggest that the increased risk of tobacco use disorder in adolescents with ADHD may not be attributable to a greater reinforcing efficacy of nicotine, and that other aspects of tobacco smoking (e.g., non-nicotine constituents, sensory factors) may play a more important role. A policy implication of these findings is that a nicotine standard to reduce initiation of tobacco use among adolescents in the general population may also be effective among those with ADHD.
注意力缺陷多动障碍（ADHD）是烟草使用障碍的一个独立风险因素。与没有ADHD的个体相比，患有ADHD的个体更有可能在更年轻的时候开始吸烟，更快成为每日吸烟者，每天吸更多香烟，并且表现出更强的尼古丁依赖性。目前尚不清楚这些发现是否是由于尼古丁在患有ADHD的个体中的强化效力更强。本研究的目的是使用ADHD动物模型——自发性高血压大鼠（SHR）品系来研究这个问题。
在23小时的实验时段内，让青春期SHR大鼠和Wistar（对照）大鼠按照FR 1（第1周）和FR 2（第2周）的实验安排，接触典型的强化尼古丁单位剂量（30μg/kg）、阈值强化尼古丁剂量（4μg/kg）或生理盐水，以检验自我给药的习得情况。然后通过FR递增程序评估30μg/kg剂量下的行为经济需求弹性。
在30μg/kg剂量下，与对照大鼠相比，SHR大鼠表现出更低的平均反应率、更低的主动与非主动杠杆辨别率，以及更低的获得自我给药的大鼠比例。在需求评估期间，SHR大鼠在需求强度（Q）或弹性（α；即强化效力）方面与Wistar大鼠没有显著差异。此外，在4μg/kg剂量下未观察到品系间在习得指标上的差异。
这些发现表明，患有ADHD的青少年中烟草使用障碍风险增加可能并非归因于尼古丁更强的强化效力，吸烟的其他方面（例如非尼古丁成分、感官因素）可能起更重要的作用。这些发现的一个政策含义是，在普通人群中用于减少青少年开始使用烟草的尼古丁标准，在患有ADHD的青少年中可能也有效。
