Rationale The inflammation induced by Group A Streptococcus (GAS) infection has been viewed as a vulnerability factor in mental disorders characterized by inhibitory control deficits, such as attention-deficit/hyperactivity disorder or obsessive-compulsive disorder. Antibiotic treatment reduces GAS symptoms; however, its effects on impulsivity have not been fully assessed. OBJECTIVES We investigated whether GAS exposure during early adolescence might be a vulnerability factor for adult impulsivity, if antibiotic treatment acts as a protective factor, and whether these differences are accompanied by changes in the inflammatory cytokine frontostriatal regions. METHODS Male Wistar rats were exposed to the GAS antigen or to vehicle plus adjuvants at postnatal day (PND) 35 (with two boosts), and they received either ampicillin (supplemented in the drinking water) or water alone from PND35 to PND70. Adult impulsivity was assessed using two different models, the 5-choice serial reaction time task (5-CSRT task) and the delay discounting task (DDT). The levels of interleukin-6 (IL-6) and IL-17 were measured in the prefrontal cortex (PFc), and the tumor necrosis factor α levels (TNFα) were measured in the PFc and nucleus accumbens (NAcc). RESULTS GAS exposure and ampicillin treatment increased the waiting impulsivity by a higher number of premature responses when the animals were challenged by a long intertrial interval during the 5-CSRT task. The GAS exposure revealed higher impulsive choices at the highest delay (40 s) when tested by DDT, while coadministration with ampicillin prevented the impulsive choice. GAS exposure and ampicillin reduced the IL-6 and IL-17 levels in the PFc, and ampicillin treatment increased the TNFα levels in the NAcc. A regression analysis revealed a significant contribution of GAS exposure and TNFα levels to the observed effects. CONCLUSIONS GAS exposure and ampicillin treatment induced an inhibitory control deficit in a different manner depending on the form of impulsivity measured here, with inflammatory long-term changes in the PFc and NAcc that might increase the vulnerability to impulsivity-related neuropsychiatric disorders.

中文翻译：

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大鼠链球菌抗原暴露和抗生素治疗后对冲动行为的易感性增加

基本原理 A 组链球菌 (GAS) 感染引起的炎症已被视为以抑制控制缺陷为特征的精神障碍的脆弱因素，例如注意力缺陷/多动障碍或强迫症。抗生素治疗可减轻 GAS 症状；然而，它对冲动的影响尚未得到充分评估。目标我们调查了青春期早期的 GAS 暴露是否可能是成人冲动的易感因素，如果抗生素治疗起到保护因素的作用，以及这些差异是否伴随着炎性细胞因子额纹状体区域的变化。方法 雄性 Wistar 大鼠在出生后第 35 天 (PND) 暴露于 GAS 抗原或载体加佐剂（两次加强），他们接受了氨苄青霉素（在饮用水中补充）或单独的水，从 PND35 到 PND70。使用两种不同的模型评估成人冲动性，即 5 项选择系列反应时间任务（5-CSRT 任务）和延迟折扣任务（DDT）。在前额叶皮层 (PFc) 中测量了白介素 6 (IL-6) 和 IL-17 的水平，在 PFc 和伏隔核 (NAcc) 中测量了肿瘤坏死因子 α 水平 (TNFα)。结果 当动物在 5-CSRT 任务期间受到长间隔的挑战时，GAS 暴露和氨苄青霉素治疗会通过更多的过早反应增加等待冲动。当通过 DDT 测试时，GAS 暴露在最高延迟（40 秒）显示更高的冲动选择，而与氨苄西林共同给药阻止了冲动选择。GAS 暴露和氨苄西林降低了 PFc 中的 IL-6 和 IL-17 水平，氨苄西林治疗增加了 NAcc 中的 TNFα 水平。回归分析揭示了 GAS 暴露和 TNFα 水平对观察到的影响的显着贡献。结论 GAS 暴露和氨苄西林治疗以不同方式诱导抑制控制缺陷，具体取决于此处测量的冲动形式，PFc 和 NAcc 的炎症长期变化可能会增加冲动相关神经精神疾病的易感性。