Adolescent cocaine exposure enhances the GABAergic transmission in the prelimbic cortex of adult mice
Adolescent cocaine exposure enhances the GABAergic transmission in the prelimbic cortex of adult mice
复制标题
青少年可卡因暴露增强成年小鼠前边缘皮层的 GABA 能传递
DOI：
10.1096/fj.201802192rr
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发表时间：
2019-07-01
期刊：
影响因子：
4.8
通讯作者：
Guan, Xiaowei
中科院分区：
文献类型：
--
作者：
Shi, Pengbo;Nie, Jiaxun;Guan, Xiaowei
我们最近在大鼠中发现，青少年可卡因暴露诱导内侧前额叶皮层（mPFC）突触的长期修饰，这可能有助于成年后的长期行为结果。在本研究中，我们进一步研究了青少年可卡因成瘾相关的精神问题的分子机制，特别是关注mPFC的一个亚区--边缘前皮质（PrL）的GABA能传递的改变。与先前的研究一致，青少年可卡因暴露小鼠在成年期表现出增强的焦虑样行为。在相同的小鼠模型中，抑郁样行为也增加了，但条件性位置偏爱形成正常。与此同时，活动的锥体神经元在第V层的PrL青少年可卡因暴露后减少，伴随着在成年小鼠的PrL对称突触的百分比增加。此外，微型抑制性突触后电流，而不是微型兴奋性突触后电流的增加，这些锥体神经元，并增加GABA的水平被发现在成人PrL。成人PrL中GABA能系统中的分子也因青少年可卡因使用而改变，如谷氨酸脱羧酶67 kDa、GABA（A）-α 1增加和GABA转运蛋白1减少所示。在相同的小鼠中，GABA能传递的一些调节因子如神经调节蛋白1/ErbB 4信号也被增强。总的来说，这些研究结果表明，青少年可卡因暴露导致PrL锥体神经元上GABA能传递的永久增强，随后减弱了这些神经元的活动，并最终导致晚年精神疾病的发展。施，P。，聂，J.，刘洪，李，Y.，卢，X.，沈，X.，Ge，F.，袁，T.- F.、Guan，X.青少年可卡因暴露增强了成年小鼠边缘前皮质中GABA能的传递。
We have recently shown in rats that adolescent cocaine exposure induces prolonged modifications on synapses in medial prefrontal cortex (mPFC), which might contribute to long-term behavioral outcomes in adulthood. In this study, we further investigated the molecular mechanisms underlying adolescent cocaine exposure-related psychiatric problems in adulthood, especially focusing on the alterations of GABAergic transmission in prelimbic cortex (PrL), 1 subregion of mPFC. Consistent with a previous study, adolescent cocaine-exposed mice exhibited enhanced anxiety-like behaviors in their adulthood. In the same mice models, depression-like behaviors increased as well, but the conditioned place preference formed normally. In parallel, activities of pyramidal neurons at layer V of PrL were reduced after adolescent cocaine exposure, accompanied by an increase in the percentage of symmetric synapses in PrL of adult mice. Additionally, miniature inhibitory postsynaptic currents rather than miniature excitatory postsynaptic currents were increased on these pyramidal neurons, and increased levels of GABA were found in adult PrL. The molecules in the GABAergic system in adult PrL were also changed by adolescent cocaine use, as indicated by increased glutamate decarboxylase 67 kDa, GABA(A)-alpha 1, and decreased GABA transporter 1. In the same mice, some regulators to GABAergic transmission such as neuregulin 1/ErbB4 signals were heightened as well. Collectively, these findings revealed that adolescent cocaine exposure results in permanent enhancement of GABAergic transmission on pyramidal neurons in PrL, which subsequently attenuate the activities of these neurons and ultimately contributes to the development of psychiatric disorders in later life.-Shi, P., Nie, J., Liu, H., Li, Y., Lu, X., Shen, X., Ge, F., Yuan, T.-F., Guan, X. Adolescent cocaine exposure enhances the GABAergic transmission in the prelimbic cortex of adult mice.