Department of Neuroscience, The Scripps Research Institute, La Jolla, California.
Department of Psychiatry, University of California, La Jolla, California.
Br J Pharmacol. 2020 Jan;177(1):188-203. doi: 10.1111/bph.14856. Epub 2019 Oct 31.
Adolescents are regularly exposed to ∆ -tetrahydrocannabinol (THC) via smoking and, more recently, vaping cannabis extracts. Growing legalization of cannabis for medical and recreational purposes, combined with decreasing perceptions of harm, makes it increasingly important to determine the consequences of frequent adolescent exposure for motivated behaviour and lasting tolerance in response to THC.
Male and female rats inhaled THC vapour, or that from the propylene glycol (PG) vehicle, twice daily for 30 min from postnatal day (PND) 35-39 and PND 42-46 using an e-cigarette system. Thermoregulatory responses to vapour inhalation were assessed by radio-telemetry during adolescence and from PND 86-94. Chow intake was assessed in adulthood. Blood samples were obtained from additional adolescent groups following initial THC inhalation and after 4 days of twice daily exposure. Additional groups exposed repeatedly to THC or PG during adolescence were evaluated for intravenous self-administration of oxycodone as adults.
Female, not male, adolescents developed tolerance to the hypothermic effects of THC inhalation in the first week of repeated exposure despite similar plasma THC levels. Each sex exhibited tolerance to THC hypothermia in adulthood after repeated adolescent THC. However, enhanced potency was found in females. Repeated THC male rats consumed more food than their PG-treated control group, without significant bodyweight differences. Adolescent THC did not alter oxycodone self-administration in either sex but increased fentanyl self-administration in females.
Repeated THC vapour inhalation in adolescent rats has lasting consequences observable in adulthood.
青少年经常通过吸烟，最近还通过吸食大麻提取物来接触 ∆ -四氢大麻酚（THC）。随着大麻用于医疗和娱乐目的的合法化不断增加，以及对危害的认知不断降低，确定青少年频繁接触 THC 对动机行为和持久耐受的后果变得越来越重要。
雄性和雌性大鼠从出生后第 35-39 天和第 42-46 天开始，每天两次通过电子烟系统吸入 THC 蒸气或丙二醇（PG）载体蒸气 30 分钟，直到青春期和从 PND 86-94。通过无线电遥测术在青春期和成年期评估蒸气吸入的体温调节反应。在成年期评估食物摄入量。在初次吸入 THC 后和在每天两次暴露 4 天后，从另外的青春期组获得血液样本。在青春期期间反复暴露于 THC 或 PG 的其他组在成年后接受静脉内氧可酮自我给药评估。
尽管血浆 THC 水平相似，但只有雌性而非雄性青少年在反复暴露的第一周内对 THC 吸入的降温作用产生了耐受性。在反复的青少年 THC 暴露后，每个性别在成年后都对 THC 产生了降温作用的耐受性。但是，在雌性中发现了增强的效力。反复的 THC 雄性大鼠比其 PG 处理的对照组消耗更多的食物，但体重差异无统计学意义。青少年 THC 并未改变两性的氧可酮自我给药，但增加了雌性的芬太尼自我给药。
在青春期大鼠中反复吸入 THC 蒸气会产生可在成年期观察到的持久后果。
