Wang X, Dow-Edwards D, Anderson V, Minkoff H, Hurd Y L
Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institute, Stockholm, Sweden.
Pharmacogenomics J. 2006 Jul-Aug;6(4):255-64. doi: 10.1038/sj.tpj.6500375. Epub 2006 Feb 14.
Fetal development is a period sensitive to environmental influences such as maternal drug use. The most commonly used illicit drug by pregnant women is marijuana. The present study investigated the effects of in utero marijuana exposure on expression levels of opioid-related genes in the human fetal forebrain in light of the strong interaction between the cannabinoid and opioid systems. The study group consisted of 42 midgestation fetuses from saline-induced voluntary abortions. The opioid peptide precursors (preprodynorphin and preproenkephalin (PENK)) and receptor (mu, kappa and delta) mRNA expression were assessed in distinct brain regions. The effect of prenatal cannabis exposure was analyzed by multiple regression controlling for confounding variables (maternal alcohol and cigarette use, fetal age, sex, growth measure and post-mortem interval). Prenatal cannabis exposure was significantly associated with increased mu receptor expression in the amygdala, reduced kappa receptor mRNA in mediodorsal thalamic nucleus and reduced preproenkephalin expression in the caudal putamen. Prenatal alcohol exposure primarily influenced the kappa receptor mRNA with reduced levels in the amygdala, claustrum, putamen and insula cortex. No significant effect of prenatal nicotine exposure could be discerned in the present study group. These results indicate that maternal cannabis and alcohol exposure during pregnancy differentially impair opioid-related genes in distinct brain circuits that may have long-term effects on cognitive and emotional behaviors.
胎儿发育是一个对环境影响敏感的时期，如母亲使用药物。孕妇最常用的非法药物是大麻。鉴于大麻素系统和阿片类系统之间的强烈相互作用，本研究调查了子宫内暴露于大麻对人类胎儿前脑阿片类相关基因表达水平的影响。研究组由42例因生理盐水引产的中期妊娠胎儿组成。在不同脑区评估阿片肽前体（前强啡肽原和前脑啡肽原（PENK））和受体（μ、κ和δ）的mRNA表达。通过多元回归分析控制混杂变量（母亲饮酒和吸烟情况、胎儿年龄、性别、生长指标和死后间隔时间）来分析产前大麻暴露的影响。产前大麻暴露与杏仁核中μ受体表达增加、丘脑背内侧核中κ受体mRNA减少以及尾壳核中前脑啡肽原表达减少显著相关。产前酒精暴露主要影响κ受体mRNA，杏仁核、屏状核、壳核和岛叶皮质中的水平降低。在本研究组中未发现产前尼古丁暴露有显著影响。这些结果表明，孕期母亲接触大麻和酒精会对不同脑回路中的阿片类相关基因产生不同程度的损害，这可能对认知和情感行为产生长期影响。
