Reelin deficiency contributes to long-term behavioral abnormalities induced by chronic adolescent exposure to Δ9-tetrahydrocannabinol in mice.
Reelin deficiency contributes to long-term behavioral abnormalities induced by chronic adolescent exposure to Δ9-tetrahydrocannabinol in mice.
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DOI：
10.1016/j.neuropharm.2021.108495
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发表时间：
2021-04-01
影响因子：
4.7
通讯作者：
Telese F
中科院分区：
文献类型：
--
作者：
Iemolo A;Montilla-Perez P;Nguyen J;Risbrough VB;Taffe MA;Telese F
大麻的使用在青少年中很普遍，并与神经认知功能的长期负面结果有关。然而，对造成大麻使用长期有害影响的因素仍然知之甚少。在这里，我们研究了Reelin缺乏症如何影响青春期暴露于大麻的小鼠的行为。Reelin是一种与大脑发育和精神疾病有关的基因。为此，在青春期期间，用高剂量（10 mg/kg）的Δ9-四氢大麻酚（THC）（大麻的主要精神活性成分）长期注射表达降低水平的Reelin的杂合Reeler（HR）小鼠。在最后一次注射THC后两周，用多种行为测定法测试小鼠，包括工作记忆、社会互动、运动活动、焦虑样反应、应激反应和前脉冲抑制。与野生型（WT）相比，用THC治疗的HR小鼠表现出社会行为受损、去抑制表型升高以及对厌恶情况的反应性以性别特异性方式增加。总的来说，这些研究结果表明，Reelin缺乏会影响青春期大量消耗THC引起的行为异常，并表明阐明Reelin信号传导将提高我们对与精神疾病发展相关的行为特征的神经生物学机制的理解。
Cannabis use is widespread among adolescents and has been associated with long-term negative outcomes on neurocognitive functions. However, the factors that contribute to the long-term detrimental effects of cannabis use remain poorly understood. Here, we studied how Reelin deficiency influences the behavior of mice exposed to cannabis during adolescence. Reelin is a gene implicated in the development of the brain and of psychiatric disorders. To this aim, heterozygous Reeler (HR) mice, that express reduced level of Reelin, were chronically injected during adolescence with high doses (10mg/kg) of Δ9-tetrahydrocannabinol (THC), a major psychoactive component of cannabis. Two weeks after the last injection of THC, mice were tested with multiple behavioral assays, including working memory, social interaction, locomotor activity, anxiety-like responses, stress reactivity, and pre-pulse inhibition. Compared to wild-type (WT), HR mice treated with THC showed impaired social behaviors, elevated disinhibitory phenotypes and increased reactivity to aversive situations, in a sex-specific manner. Overall, these findings show that Reelin deficiency influences behavioral abnormalities caused by heavy consumption of THC during adolescence and suggest that elucidating Reelin signaling will improve our understanding of neurobiological mechanisms underlying behavioral traits relevant to the development of psychiatric conditions.
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DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
4.5
作者：
HUBER, PJ
通讯作者：
HUBER, PJ
影响因子：
7.6
作者：
Flagel, Shelly B.;Robinson, Terry E.;Clark, Jeremy J.;Clinton, Sarah M.;Watson, Stanley J.;Seeman, Phillip;Phillips, Paul E. M.;Akil, Huda
通讯作者：
Akil, Huda
影响因子：
6.7
作者：
Abrams, D. I.;Vizoso, H. P.;Benowitz, N. L.
通讯作者：
Benowitz, N. L.
影响因子：
3.2
作者：
Habl, Gregor;Schmitt, Andrea;Falkai, Peter
通讯作者：
Falkai, Peter