Gellner Candice A, Carreño Diana, Belluzzi James D, Leslie Frances M
Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University of California, Irvine, Irvine, CA, United States.
Front Psychiatry. 2023 Feb 6;14:1096213. doi: 10.3389/fpsyt.2023.1096213. eCollection 2023.
Given the rapid increase in teen vaping over recent years it is critical to understand mechanisms underlying addiction and relapse to tobacco use at this age. To evaluate the role of non-nicotine constituents in cigarette smoke, our lab has previously established a model of intravenous self-administration of aqueous cigarette smoke extract (CSE). We now compare the sensitivity of male adolescent and adult rats who have self-administered CSE or nicotine to reinstatement with the pharmacological stressor, yohimbine, with and without cues.
Adolescents and adults, aged postnatal day (P) 34 and 84, were tested for the effect of yohimbine (0-2.5 mg/kg) on plasma corticosterone levels to establish a dose that was an effective stressor at both ages. Separate groups of animals were trained to lever press for food before beginning 1-hour drug self-administration sessions for nicotine or CSE (15 μg/kg/infusion nicotine content). Once stable responding was reached, drug was removed, and behavior extinguished. Drug-seeking behavior was reinstated with yohimbine, cues, or a combination of yohimbine and cues.
Although adolescents and adults showed different dose-responses for yohimbine-induced corticosterone release, a dose of 2.5 mg/kg increased stress hormone levels at both ages. Whereas both ages displayed similar responding for CSE and nicotine, adolescents self-administered more CSE and nicotine as compared to adults. Cues and cues + stress reinstated responding to a greater extent in animals that had self-administered CSE, regardless of age.
These findings suggest that non-nicotine tobacco smoke constituents influence later but not earlier stages of addiction in both adolescent and adult male rats.
鉴于近年来青少年电子烟使用的迅速增加，了解这个年龄段烟草成瘾和复吸的潜在机制至关重要。为了评估香烟烟雾中非尼古丁成分的作用，我们实验室先前建立了一个静脉注射香烟烟雾提取物（CSE）自我给药的模型。我们现在比较自我给药CSE或尼古丁的雄性青少年和成年大鼠对药理学应激源育亨宾恢复用药的敏感性，有无线索提示的情况均进行了比较。
对出生后第34天（P34）和第84天的青少年和成年大鼠进行测试，观察育亨宾（0 - 2.5毫克/千克）对血浆皮质酮水平的影响，以确定一个在两个年龄段均有效的应激剂量。在开始为期1小时的尼古丁或CSE（每输注含15微克/千克尼古丁）药物自我给药实验之前，将单独的动物组训练为按压杠杆获取食物。一旦达到稳定反应，停止给药并消除行为。通过育亨宾、线索提示或育亨宾与线索提示的组合来恢复觅药行为。
尽管青少年和成年大鼠对育亨宾诱导的皮质酮释放表现出不同的剂量反应，但2.5毫克/千克的剂量在两个年龄段均增加了应激激素水平。虽然两个年龄段对CSE和尼古丁的反应相似，但与成年大鼠相比，青少年自我给药的CSE和尼古丁更多。无论年龄大小，线索提示以及线索提示 + 应激在自我给药CSE的动物中恢复反应的程度更大。
这些发现表明，非尼古丁烟草烟雾成分影响成年和青少年雄性大鼠成瘾的后期而非早期阶段。
