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首页> 美国卫生研究院文献>Neuropsychopharmacology >Binge-Like Alcohol Exposure During Adolescence Disrupts Dopaminergic Neurotransmission in the Adult Prelimbic Cortex
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Binge-Like Alcohol Exposure During Adolescence Disrupts Dopaminergic Neurotransmission in the Adult Prelimbic Cortex

机译：青春期的暴饮暴食会破坏成年前皮质的多巴胺能神经传递。

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Repeated binge-like exposure to alcohol during adolescence has been reported to perturb prefrontal cortical development, yet the mechanisms underlying these effects are unknown. Here we report that adolescent intermittent ethanol exposure induces cellular and dopaminergic abnormalities in the adult prelimbic cortex (PrL-C). Exposing rats to alcohol during early-mid adolescence (PD28–42) increased the density of long/thin dendritic spines of layer 5 pyramidal neurons in the adult PrL-C. Interestingly, although AIE exposure did not alter the expression of glutamatergic proteins in the adult PrL-C, there was a pronounced reduction in dopamine (DA) D1 receptor modulation of both intrinsic firing and evoked NMDA currents in pyramidal cells, whereas D2 receptor function was unaltered. Recordings from fast-spiking interneurons also revealed that AIE reduced intrinsic excitability, glutamatergic signaling, and D1 receptor modulation of these cells. Analysis of PrL-C tissue of AIE-exposed rats further revealed persistent changes in the expression of DA-related proteins, including reductions in the expression of tyrosine hydroxylase and catechol-O-methyltransferase (COMT). AIE exposure was associated with hypermethylation of the COMT promoter at a conserved CpG site in exon II. Taken together, these findings demonstrate that AIE exposure disrupts DA and GABAergic transmission in the adult medial prefrontal cortex (mPFC). As DA and GABA work in concert to shape and synchronize neuronal ensembles in the PFC, these alterations could contribute to deficits in behavioral control and decision-making in adults who abused alcohol during adolescence.
机译：据报道，青春期反复暴饮暴食会扰乱前额叶皮质的发育，但这些作用的潜在机制尚不清楚。在这里，我们报告青少年间歇性乙醇暴露在成人前缘皮质（PrL-C）中诱导细胞和多巴胺能异常。在成年中早期（PD28-42）期间，将大鼠暴露于酒精中会增加成年PrL-C中第5层锥体神经元的长/细树突棘的密度。有趣的是，尽管AIE暴露并没有改变成年PrL-C中谷氨酸能蛋白的表达，但锥体细胞内源性放电和诱发的NMDA电流的多巴胺（DA）D1受体调节显着降低，而D2受体的功能却是保持不变。快速掺入的中间神经元的记录还显示，AIE降低了这些细胞的内在兴奋性，谷氨酸能信号传导和D1受体调节。对暴露于AIE的大鼠的PrL-C组织的分析进一步揭示了DA相关蛋白表达的持续变化，包括酪氨酸羟化酶和儿茶酚-O-甲基转移酶（COMT）的表达降低。 AIE暴露与外显子II中保守CpG位点COMT启动子的高甲基化有关。综上所述，这些发现表明，AIE暴露破坏了成人内侧前额叶皮层（mPFC）中的DA和GABA能传递。由于DA和GABA共同作用以塑造和同步PFC中的神经元集成，这些改变可能导致青春期滥用酒精的成年人的行为控制和决策缺陷。

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