Department of Pharmaceutical Sciences, College of Health Sciences, University of California, Irvine, Irvine, CA, USA.
Department of Pathology and Laboratory Medicine, School of Medicine, University of California, Irvine, Irvine, CA, USA.
Nicotine Tob Res. 2022 Jul 13;24(8):1186-1192. doi: 10.1093/ntr/ntab218.
Initiation of tobacco products typically occurs in adolescence. Adolescence is a critical period in development where the maturation of brain neurocircuitry is vulnerable to nicotine. Nicotine-containing products and psychostimulants, such as methamphetamine (METH), are often coabused. Rodent studies have shown that nicotine exposure in early adolescence increases subsequent drug intake and reward. Given the exponential increase in e-cigarette use among adolescents, there is a pressing need to understand whether adolescent nicotine exposure impacts concurrent increased METH use. The objective of this study is to evaluate age, sex, and longitudinal effects of nicotine pretreatment on METH reinforcement.
Male and female Sprague-Dawley rats were pretreated with a subchronic, low-dose nicotine (2×, 30 µg/kg/0.1 mL, intravenous) or saline during early adolescence (postnatal days [PN] 28-31) or adulthood (PN 86-89). Following nicotine pretreatment, on PN 32 or PN 90, animals underwent operant intravenous self-administration for METH (20 µg/kg/inf) over a 2-hour period for five consecutive days.
Early adolescent nicotine exposure enhances intravenous METH self-administration in male, but not female adolescents. Male adult rats self-administer METH over the 5-day testing period, independent of nicotine exposure. In contrast, nicotine exposure increases METH self-administration in female adults during the later sessions of the 5-day testing period.
Taken together, our data highlight age- and sex-dependent effects of low dose, subchronic nicotine pretreatment on subsequent intravenous METH self-administration.
A majority of polysubstance users begin smoking before the age of 18. Mounting evidence highlights adolescent susceptibility to nicotine exposure on brain and behavior. With the escalation in nicotine-containing products and stimulant use among adolescents, it is important to identify the consequences from adolescent nicotine use, including polysubstance use. Our study provides evidence that adolescent nicotine exposure enhances subsequent METH use, with important sex- and age-dependent effects.
烟草制品的使用通常始于青少年时期。青少年时期是大脑神经回路发育的关键时期，此时大脑神经回路容易受到尼古丁的影响。含有尼古丁的产品和精神兴奋剂，如冰毒（METH），经常被同时滥用。啮齿动物研究表明，青少年早期暴露于尼古丁会增加随后的药物摄入和奖励。鉴于青少年电子烟使用呈指数级增长，迫切需要了解青少年时期的尼古丁暴露是否会影响同时增加的 METH 使用。本研究旨在评估尼古丁预处理对 METH 强化作用的年龄、性别和纵向影响。
雄性和雌性 Sprague-Dawley 大鼠在青少年早期（出生后第 28-31 天）或成年期（第 86-89 天）接受亚慢性、低剂量尼古丁（2×，30μg/kg/0.1ml，静脉内）或盐水预处理。在尼古丁预处理后，动物在 PN32 或 PN90 时接受 2 小时内连续 5 天的 METH（20μg/kg/次）静脉内自我给药。
青少年早期暴露于尼古丁会增强雄性青少年的静脉内 METH 自我给药，但不会增强雌性青少年的静脉内 METH 自我给药。雄性成年大鼠在整个 5 天测试期内自行给予 METH，与尼古丁暴露无关。相比之下，尼古丁暴露会增加成年雌性大鼠在 5 天测试期后期的 METH 自我给药。
综上所述，我们的数据突出了低剂量、亚慢性尼古丁预处理对随后的静脉内 METH 自我给药的年龄和性别依赖性影响。
大多数多药使用者在 18 岁之前开始吸烟。越来越多的证据强调了青少年对尼古丁暴露对大脑和行为的易感性。随着青少年中含有尼古丁的产品和兴奋剂使用的增加，确定青少年时期使用尼古丁的后果非常重要，包括多药使用。我们的研究提供了证据表明，青少年时期的尼古丁暴露会增强随后的 METH 使用，并且具有重要的性别和年龄依赖性影响。
