Behavioural Neuroscience Laboratory, Neuropsychopharmacology Division, Faculty of Science and Health, School of Psychology, Dublin City University, Glasnevin, D09 W6Y4 Dublin, Ireland.
Int J Mol Sci. 2021 Sep 15;22(18):9989. doi: 10.3390/ijms22189989.
The endocannabinoid system plays a central role in the earliest stages of embryonic, postnatal and adolescent neurodevelopment. Aberrant activity of this system at key developmental phases has been shown to affect neural development. The aim of this review is to synthesise and analyse preclinical insights within rodent populations, focusing on the effects that perinatal (embryonic, gestational and early postnatal developmental stages) and adolescent (postnatal day 21-60) cannabinoid exposure impose across time on the subsequent activity of various drugs of abuse. Results in rodents show that exposure to cannabinoids during the perinatal and adolescent period can lead to multifaceted behavioural and molecular changes. In the perinatal period, significant effects of Δ-THC exposure on subsequent opiate and amphetamine reward-related behaviours were observed primarily in male rodents. These effects were not extended to include cocaine or alcohol. In adolescence, various cannabinoid agonists were used experimentally. This array of cannabinoids demonstrated consistent effects on opioids across sex. In contrast, no significant effects were observed regarding the future activity of amphetamines and cocaine. However, these studies focused primarily on male rodents. In conclusion, numerous gaps and limitations are apparent in the current body of research. The sparsity of studies analysing the perinatal period must be addressed. Future research within both periods must also focus on delineating sex-specific effects, moving away from a male-centric focus. Studies should also aim to utilise more clinically relevant cannabinoid treatments.
内源性大麻素系统在胚胎期、产后和青少年神经发育的早期阶段发挥着核心作用。该系统在关键发育阶段的异常活动已被证明会影响神经发育。本综述的目的是综合和分析啮齿动物群体中的临床前研究结果，重点关注围产期（胚胎期、妊娠期和新生儿早期发育阶段）和青少年期（出生后第 21-60 天）大麻素暴露对随后各种滥用药物的后续活性的跨时间影响。啮齿动物的研究结果表明，在围产期和青少年期接触大麻素会导致多方面的行为和分子变化。在围产期，观察到 Δ-THC 暴露对随后的阿片类药物和安非他命奖赏相关行为的显著影响主要发生在雄性啮齿动物中。这些影响并未扩展到包括可卡因或酒精。在青少年时期，实验中使用了各种大麻素激动剂。这一系列大麻素在跨性别方面对阿片类药物表现出一致的影响。相比之下，对于安非他命和可卡因的未来活动没有观察到显著影响。然而，这些研究主要集中在雄性啮齿动物上。总之，目前的研究中存在许多空白和局限性。必须解决分析围产期的研究稀疏问题。两个时期的未来研究还必须侧重于描绘性别特异性影响，摆脱以男性为中心的焦点。研究还应旨在利用更具临床相关性的大麻素治疗方法。
