Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA.
Nicotine Tob Res. 2020 Jul 16;22(8):1364-1373. doi: 10.1093/ntr/ntaa084.
During adolescence, exposure to nicotine or cannabis independently induces effects on neuromaturation and later cognitive function. However, the potential effect of both drugs under co-use conditions has become of increasing concern given the prevalence of e-cigarettes, legalization of cannabis, and availability of synthetic "spice" cannabinoid agonists.
The current studies investigated the effects of exposure to a cannabinoid receptor agonist (WIN55,212-2) and/or nicotine over a discrete time period in mid-adolescence on later intravenous nicotine self-administration in adult male and female mice. We further examined whether cannabinoid agonist administration in adulthood would alter nicotine reinforcement, with either acute or chronic pairing across 7 days.
We found that adult males exhibited increased nicotine self-administration at a lower, rewarding nicotine dose following adolescent cannabinoid exposure, either alone or with nicotine coadministration. In contrast, adult females demonstrated an opposing effect in which adolescent cannabinoid and nicotine coexposure resulted in decreased nicotine intake compared with the nicotine only and control groups. Furthermore, after maintaining nicotine self-administration across sessions, pretreatment with a low dose of the cannabinoid agonist decreased nicotine intake in both male and female control mice, and this lowering effect was evidenced after both acute and chronic treatment. However, the cannabinoid agonist was ineffective in altering nicotine intake in mice previously exposed to nicotine, cannabinoid agonist, or both during adolescence.
These data provide evidence that adolescent drug exposure can alter later nicotine reinforcement in a sex-specific manner and can further modulate the effectiveness of interventions in reducing nicotine intake during adulthood.
These studies demonstrate a significant impact of nicotine, cannabinoids, or coexposure on developmental processes during adolescence. Differential effects were observed within each sex, with opposing results found for cannabinoid exposure on nicotine intake in males and females. Intriguingly, we also evidenced resistance to the lowering effects of a cannabinoid agonist on nicotine intake in adulthood based on adolescent drug exposure. Thus, these findings have important implications for our understanding of the impact of nicotine and cannabinoids (eg, Δ9-tetrahydrocannabinol (THC) and synthetic "spice" cannabinoids) during development, with further implications for the effectiveness of therapeutic interventions based on prior drug exposure in youth.
在青少年时期，接触尼古丁或大麻会分别对神经成熟和后期认知功能产生影响。然而，鉴于电子烟的普及、大麻合法化以及合成“香料”类大麻素激动剂的可用性，人们越来越关注这两种药物在共同使用条件下的潜在影响。
本研究旨在探讨在青少年中期暴露于大麻素受体激动剂（WIN55,212-2）和/或尼古丁后，在特定时间段内对成年雄性和雌性小鼠后期静脉内尼古丁自我给药的影响。我们进一步研究了成年时给予大麻素激动剂是否会改变尼古丁的强化作用，无论是急性还是慢性，持续 7 天。
我们发现，成年雄性在青少年期暴露于大麻素后，即使在较低的、有奖励作用的尼古丁剂量下，也会增加尼古丁的自我给药。相比之下，成年雌性表现出相反的效果，即青少年期大麻素和尼古丁共同暴露导致与仅尼古丁和对照组相比，尼古丁摄入量减少。此外，在维持尼古丁自我给药的过程中，给予低剂量的大麻素激动剂会降低雄性和雌性对照组小鼠的尼古丁摄入量，这种降低作用在急性和慢性治疗后都有证据。然而，在之前暴露于尼古丁、大麻素激动剂或两者的青少年时期的小鼠中，大麻素激动剂对尼古丁摄入量没有影响。
这些数据提供了证据表明，青少年期的药物暴露可以以性别特异性的方式改变后期尼古丁的强化作用，并进一步调节成年期减少尼古丁摄入的干预措施的有效性。
这些研究表明，尼古丁、大麻素或共同暴露对青少年时期的发育过程有重大影响。在每个性别中都观察到了不同的影响，对于男性和女性，大麻素暴露对尼古丁摄入量的影响结果相反。有趣的是，我们还发现，基于青少年期的药物暴露，对大麻素激动剂降低尼古丁摄入量的作用产生了耐药性。因此，这些发现对我们理解尼古丁和大麻素（例如 Δ9-四氢大麻酚（THC）和合成“香料”类大麻素）在发育过程中的影响具有重要意义，并进一步影响基于青年时期药物暴露的治疗干预措施的有效性。
