Effects of adolescent cannabinoid administration in mice on behavioural inhibition and susceptibility to stress during adulthood

Armaan Fallahi, Giovanni Hernandez, Jose-Maria Restrepo Lozano, Cecilia Flores
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Abstract

Background: Cannabis is one of the most frequently used substances by adolescents. Early exposure to psychoactive compounds has been shown to alter normal brain development and has consequences for psychiatric illness and behaviour in adulthood. In this study, we explored the effects of adolescent synthetic cannabinoid exposure on susceptibility to stress in adulthood, in addition to changes in impulsive behaviour. Methods: Chronic treatment with synthetic cannabinoid WIN55,212-2 (WIN) at various doses in adolescent mice was followed by the chronic social defeat stress paradigm in adulthood to assay changes in susceptibility to stress. We then employed the operant Go/No-Go task to investigate changes in impulsivity. Results: No changes in susceptibility to stress were identified (χ2(3)=0.585, p=0.900). Strikingly, we demonstrated a dose dependent decrease in impulsivity of adolescent WIN-treated subjects as measured using the Go/No-Go task (F(3, 20)=5.743, p=0.0053). Limitations: The main limitation of our findings is the small sample size, particularly for assaying changes in susceptibility to stress using the chronic social defeat stress paradigm. Furthermore, the single housing of animals and suboptimal performance of controls may have affected our findings in the Go/No-Go task. Conclusion: Overall, this study presents a novel behavioural finding consequent to adolescent exposure to cannabinoids. Further research into the long-term effects of cannabinoid use in adolescence is needed, especially in light of its prevalent use and legalization in Canada.
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青少年大麻素对成年期小鼠行为抑制和应激易感性的影响
背景:大麻是青少年最常使用的物质之一。早期接触精神活性化合物已被证明会改变正常的大脑发育,并对成年后的精神疾病和行为产生影响。在这项研究中,我们探讨了青少年合成大麻素暴露对成年后压力易感性的影响,以及冲动行为的变化。方法:用不同剂量的合成大麻素WIN55212-2(WIN)对青春期小鼠进行慢性治疗,然后采用成年后的慢性社会失败应激模式来测定应激易感性的变化。然后,我们采用可操作的“去/不去”任务来调查冲动的变化。结果:没有发现应激易感性的变化(χ2(3)=0.585,p=0.900)。引人注目的是,我们证明了青少年WIN治疗受试者的冲动性在使用Go/No-Go任务测量时呈剂量依赖性降低(F(3,20)=5.743,p=0.0053)。局限性:我们发现的主要局限性是样本量小,特别是使用慢性社会失败压力范式来分析压力易感性的变化。此外,动物的单一饲养和控制的次优表现可能影响了我们在Go/No-Go任务中的发现。结论:总的来说,这项研究提供了一个新的行为发现,青少年接触大麻素。需要进一步研究青少年使用大麻素的长期影响,特别是考虑到它在加拿大的广泛使用和合法化。
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