Abstract: 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 ? levels (TNF?) 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 TNF? levels in the NAcc. A regression analysis revealed a significant contribution of GAS exposure and TNF? 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.

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