Toluene is an organic solvent commonly misused by inhalation among adolescents to experience psychoactive effects. Repeated toluene exposure produces several cognitive deficits, including working memory impairment in which the medial prefrontal cortex (mPFC) plays a central role. Among other effects, toluene antagonizes NMDA receptors, enhance GABAA receptor-mediated responses and increases dopamine release. We have recently reported that animals repeatedly exposed to toluene show increased mPFC excitability; however, alterations in synaptic transmission, including long-term synaptic plasticity of glutamatergic responses have not been studied thus far. Here we used extracellular recordings to determine the effects of repeated toluene exposure (8000 ppm for 30 min, twice a day, for ten days) on the synaptic transmission converging on prelimbic layer 5 pyramidal neurons of the mPFC in adolescent male Wistar rats. Repeated toluene exposure increased mPFC's synaptic strength and reduced the inhibitory transmission assessed by input-output curves and paired-pulse inhibition protocols, respectively. Both toluene and a selective D1 receptor antagonist blocked the ability of exogenous dopamine to induce synaptic potentiation. Repeated toluene exposure also altered the ability of NMDA to induce synaptic depression of excitatory transmission. Taken together, the changes in synaptic strength and impairment of the NMDA-mediated plasticity of the mPFC demonstrate a series of synaptic modifications of the glutamatergic transmission that may underlie the cognitive impairment resulting from repeated toluene exposure.

中文翻译：

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重复暴露于甲苯会改变第5层内侧前额叶皮层的突触传递。

甲苯是一种有机溶剂，通常会因青少年吸入而误用，以产生精神活性。反复接触甲苯会产生一些认知缺陷，包括工作记忆障碍，其中前额叶内侧皮层（mPFC）发挥着核心作用。除其他作用外，甲苯可拮抗NMDA受体，增强GABAA受体介导的反应并增加多巴胺释放。我们最近报道说，反复接触甲苯的动物表现出mPFC兴奋性增加。然而，迄今为止尚未研究突触传递的改变，包括谷氨酸能反应的长期突触可塑性。在这里，我们使用细胞外记录来确定重复暴露于甲苯的影响（每天两次，每次8000 ppm，持续30分钟，持续十天），在青春期Wistar大鼠的mPFC的前缘5层锥体神经元上的突触传递上。反复接触甲苯会增加mPFC的突触强度，并降低分别通过输入-输出曲线和成对脉冲抑制方案评估的抑制传递。甲苯和选择性的D1受体拮抗剂都阻断外源多巴胺诱导突触增强的能力。重复的甲苯暴露也改变了NMDA诱导突触传递抑制突触传递的能力。两者合计，突触强度的变化和NMDA介导的mPFC可塑性的损害表明，谷氨酸能传递的一系列突触修饰可能是由于反复接触甲苯导致的认知损害的基础。