Department of Anatomy and Neurobiology (A.M.T., Y.F., T.I.R., D.P.), Department of Biological Chemistry, (D.P.), and Department of Pharmaceutical Sciences (D.P.), University of California, Irvine, California.
Department of Anatomy and Neurobiology (A.M.T., Y.F., T.I.R., D.P.), Department of Biological Chemistry, (D.P.), and Department of Pharmaceutical Sciences (D.P.), University of California, Irvine, California
J Pharmacol Exp Ther. 2021 Sep;378(3):215-221. doi: 10.1124/jpet.121.000740. Epub 2021 Jun 28.
Evidence suggests that Δ-tetrahydrocannabinol (Δ-THC), the intoxicating component of cannabis, causes enduring changes in the structure and function of adolescent brain circuits implicated in nociceptive responding. However, whether such changes might persistently disrupt nociceptive behaviors remains unknown. In the present study, we subjected C57BL6/J mice of both sexes to once-daily injections of Δ-THC (5 mg-kg, i.p.) or vehicle throughout adolescence (PND 30-43) and, when the animals had reached adulthood (PND 70), assessed nociceptive behavior using the formalin and chronic constriction injury tests. We also investigated, using the tail immersion test, the antinociceptive effects of morphine and the development of tolerance to such effects. The results show that adolescent Δ-THC exposure does not significantly impair nociceptive responding or morphine-related antinociception and tolerance. The findings suggest that frequent exposure to a moderate dose of Δ-THC during adolescence does not permanently alter nociceptive circuits in male or female mice. SIGNIFICANCE STATEMENT: The endocannabinoid system serves critical functions in the central and peripheral nervous systems, including regulation of pain, and can be modified by prolonged exposure to the intoxicating constituent of cannabis, Δ-tetrahydrocannabinol (Δ-THC). This raises the possibility that regular use of Δ-THC-containing cannabis during adolescence might cause changes in nociception that persist into adulthood. This study found that frequent early-life exposure to a moderate dose of Δ-THC does not permanently alter nociceptive function in male or female mice.
有证据表明，大麻的致醉成分Δ-四氢大麻酚（Δ-THC）会导致青少年时期参与疼痛反应的大脑回路的结构和功能发生持久变化。然而，这种变化是否会持续破坏疼痛行为尚不清楚。在本研究中，我们让 C57BL6/J 雌雄小鼠在整个青春期（PND30-43）每天接受一次Δ-THC（5mg/kg，ip）或载体注射，当动物成年（PND70）时，使用福尔马林和慢性缩窄性损伤试验评估疼痛行为。我们还使用尾巴浸入试验研究了吗啡的镇痛作用和对这种作用的耐受性的发展。结果表明，青春期Δ-THC 暴露不会显著损害疼痛反应或吗啡相关的镇痛和耐受。这些发现表明，青春期频繁暴露于中等剂量的Δ-THC 不会永久性改变雄性或雌性小鼠的疼痛回路。
内源性大麻素系统在中枢和外周神经系统中发挥着关键作用，包括对疼痛的调节，并且可以通过长时间暴露于大麻的致醉成分Δ-四氢大麻酚（Δ-THC）而改变。这就提出了这样一种可能性，即在青春期经常使用含有Δ-THC 的大麻可能会导致疼痛感知的变化，这种变化会持续到成年期。本研究发现，频繁的早期生活暴露于中等剂量的Δ-THC 不会永久性改变雄性或雌性小鼠的疼痛功能。
