Impact of early-life lead exposure on adult delta-9-tetrahydrocannabinol sensitivity in male and female C57BL6/J mice

IF 2.6 3区 医学 Q3 NEUROSCIENCES
Daniel Garcy, Stephen L. Boehm II
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引用次数: 0

Abstract

Environmental exposure to lead (Pb) and cannabis use are two of the largest public health issues facing modern society in the United States and around the world. Exposure to Pb in early life has been unequivocally shown to have negative impacts on development, and recent research is mounting showing that it may also predispose individuals for risk of developing substance use disorders (SUD). At the same time, societal and legal attitudes towards cannabis (the main psychoactive component of which is delta-9-tetrahydrocannabinol) have been shifting, and many American states have legalized the recreational use of cannabis. It is also the 3rd most widely used drug of abuse in the US, and rates of cannabis use disorder are on the rise. Here we establish a link between early life Pb exposure and later THC-related behavior in C57BL6/J mice, as has been demonstrated for other drugs of abuse. The study seeks to answer whether Pb exposure affects physiological/behavioral THC sensitivity (as measured by the cannabinoid-induced tetrad). It was hypothesized that Pb exposure would decrease THC sensitivity and that sex-dependent effects of Pb-exposure and THC would be observed. Interestingly, results showed that THC sensitivity was increased by Pb exposure, but only in female mice. Future research will fully explore the implications of these findings, namely how these effects impact THC self-administration and the mechanism(s) by which developmental Pb exposure produces these effects.

早期铅暴露对雄性和雌性C57BL6/J小鼠成年δ-9-四氢大麻酚敏感性的影响。
铅的环境暴露和大麻的使用是美国和世界各地现代社会面临的两个最大的公共卫生问题。早期接触铅已被明确证明对发育有负面影响,最近的研究表明,铅也可能使个人容易患上物质使用障碍(SUD)。与此同时,社会和法律对大麻(其主要精神活性成分是δ-9-四氢大麻酚)的态度一直在转变,美国许多州已将大麻的娱乐性使用合法化。它也是美国使用最广泛的第三大滥用药物,大麻使用障碍的发病率正在上升。在这里,我们在C57BL6/J小鼠的早期铅暴露和后期THC相关行为之间建立了联系,正如其他滥用药物所证明的那样。该研究试图回答铅暴露是否会影响生理/行为四氢大麻酚的敏感性(通过大麻素诱导的四分体测量)。假设铅暴露会降低四氢大麻酚的敏感性,并观察到铅暴露和四氢大麻醚的性别依赖性影响。有趣的是,研究结果表明,铅暴露会增加四氢大麻酚的敏感性,但仅在雌性小鼠中。未来的研究将充分探索这些发现的含义,即这些影响如何影响四氢大麻酚的自我给药,以及发育性铅暴露产生这些影响的机制。
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来源期刊
CiteScore
5.60
自引率
10.30%
发文量
48
审稿时长
58 days
期刊介绍: Neurotoxicology and Teratology provides a forum for publishing new information regarding the effects of chemical and physical agents on the developing, adult or aging nervous system. In this context, the fields of neurotoxicology and teratology include studies of agent-induced alterations of nervous system function, with a focus on behavioral outcomes and their underlying physiological and neurochemical mechanisms. The Journal publishes original, peer-reviewed Research Reports of experimental, clinical, and epidemiological studies that address the neurotoxicity and/or functional teratology of pesticides, solvents, heavy metals, nanomaterials, organometals, industrial compounds, mixtures, drugs of abuse, pharmaceuticals, animal and plant toxins, atmospheric reaction products, and physical agents such as radiation and noise. These reports include traditional mammalian neurotoxicology experiments, human studies, studies using non-mammalian animal models, and mechanistic studies in vivo or in vitro. Special Issues, Reviews, Commentaries, Meeting Reports, and Symposium Papers provide timely updates on areas that have reached a critical point of synthesis, on aspects of a scientific field undergoing rapid change, or on areas that present special methodological or interpretive problems. Theoretical Articles address concepts and potential mechanisms underlying actions of agents of interest in the nervous system. The Journal also publishes Brief Communications that concisely describe a new method, technique, apparatus, or experimental result.
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