父亲每天或间歇给 F1 和 F2 大鼠注射大麻对其神经行为的持续影响

IF 3.4 3区 医学 Q2 NEUROSCIENCES Neurotoxicology Pub Date : 2024-05-27 DOI:10.1016/j.neuro.2024.05.005
Andrew B. Hawkey , Sarabesh Natarajan , Olivia Kelly , Anas Gondal , Corinne Wells , Michelle Louise Jones , Amir H. Rezvani , Susan K. Murphy , Edward D. Levin
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引用次数: 0

摘要

我们早先在大鼠身上进行的研究表明,父亲在孕前多次单独或与大麻提取物中的其他成分一起接触Δ9-四氢大麻酚(Δ9-THC)会对其后代造成严重的神经行为损害。在本研究中,我们比较了每周连续两天每天接触大麻提取物(CE)的影响,模拟了人类周末使用大麻的情况。大麻提取物中含有Δ9-四氢大麻酚以及大麻二酚和大麻酚。我们还将该研究的调查范围扩大到祖父大麻暴露对 F2 代的跨代影响,并包括测试父亲大麻暴露对 F1 代和 F2 代后代阿片类药物自我给药反应的影响。我们复制了雄性大鼠在与药物无害的雌性大鼠交配前四周每天暴露于含有 4 毫克/千克/天 Δ9-THC 的大麻提取物的 F1 代后代中神经行为受损的研究结果。每天接触大麻提取物 4 周后,雄性大鼠的体重增加显著减少。相比之下,其后代在出生后第三至四周的体重和肛门距离(AGD)明显增加。F1 代大鼠的行为效应表现为:雌性后代在图 8 迷宫中运动活动的习惯性增加,雄性后代对阿片类药物瑞芬太尼的杠杆按压增加。F2 代的负向地心引力明显减弱,运动活动的典型性别差异消失,而 F1 代则没有这种影响。这项研究表明,父亲在交配前四周每天接触大麻会导致 F1 和 F2 后代出现明显的神经行为障碍。连续四周每周两天间歇性接触大麻也会造成类似的神经行为损害。总之,应关注父亲和母亲接触大麻对其后代神经行为发育的影响。
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Persisting neurobehavioral consequences of daily or intermittent paternal cannabis administration in F1 and F2 Rats

Repeated paternal preconception exposure to Δ9-tetrahydrocannabinol (Δ9-THC) alone or together with the other constituents in a cannabis extract has been shown in our earlier studies in rats to cause significant neurobehavioral impairment in their offspring. In the current study, we compared the effects of daily cannabis extract (CE) exposure to cannabis on two consecutive days per week, modeling weekend cannabis use in human. The CE contained Δ9-THC as well as cannabidiol and cannabinol. We also extended the investigation of the study to cross-generational effects of grand-paternal cannabis exposure on the F2 generation and included testing the effects of paternal cannabis exposure on responding for opiate self-administration in F1 and F2 generation offspring. We replicated the findings of neurobehavioral impairment in F1 offspring of male rats exposed to cannabis extract containing 4 mg/kg/day of Δ9-THC daily for four weeks prior to mating with drug naïve females. The 4-week cannabis extract exposure caused a significant decrease in weight gain in the male rats exposed daily. In contrast, their offspring showed significantly greater body weights and anogenital distances (AGD) in the third to fourth weeks after birth. The behavioral effects seen in the F1 generation were increased habituation of locomotor activity in the figure-8 maze in female offspring and increased lever pressing for the opiate drug remifentanil in male offspring. The F2 generation showed significantly impaired negative geotaxis and an elimination of the typical sex-difference in locomotor activity, with effects not seen in the F1 generation. This study shows that daily paternal cannabis exposure for four weeks prior to mating causes significant neurobehavioral impairment in the F1 and F2 offspring. Intermittent exposure on two consecutive days per week for four weeks caused comparable neurobehavioral impairment. In sum, there should be concern about paternal as well as maternal exposure to cannabis concerning neurobehavioral development of their offspring.

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来源期刊
Neurotoxicology
Neurotoxicology 医学-毒理学
CiteScore
6.80
自引率
5.90%
发文量
161
审稿时长
70 days
期刊介绍: NeuroToxicology specializes in publishing the best peer-reviewed original research papers dealing with the effects of toxic substances on the nervous system of humans and experimental animals of all ages. The Journal emphasizes papers dealing with the neurotoxic effects of environmentally significant chemical hazards, manufactured drugs and naturally occurring compounds.
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