PMID- 32798664 OWN - NLM STAT- MEDLINE DCOM- 20210427 LR - 20210427 IS - 1090-2139 (Electronic) IS - 0889-1591 (Linking) VI - 89 DP - 2020 Oct TI - Increased vulnerability to impulsive behavior after streptococcal antigen exposure and antibiotic treatment in rats. PG - 675-688 LID - S0889-1591(20)30083-0 [pii] LID - 10.1016/j.bbi.2020.08.010 [doi] AB - 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 alpha levels (TNFalpha) 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 TNFalpha levels in the NAcc. A regression analysis revealed a significant contribution of GAS exposure and TNFalpha 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. CI - Copyright (c) 2020 Elsevier Inc. All rights reserved. FAU - Mora, Santiago AU - Mora S AD - Department of Psychology and Health Research Centre, University of Almeria, Carretera de Sacramento s/n, 04120 Almeria, Spain. FAU - Martin-Gonzalez, Elena AU - Martin-Gonzalez E AD - Department of Psychology and Health Research Centre, University of Almeria, Carretera de Sacramento s/n, 04120 Almeria, Spain. FAU - Prados-Pardo, Angeles AU - Prados-Pardo A AD - Department of Psychology and Health Research Centre, University of Almeria, Carretera de Sacramento s/n, 04120 Almeria, Spain. FAU - Moreno, Joaquin AU - Moreno J AD - Department of Biology and Geology, CeiA3 and CIAMBITAL, University of Almeria, Carretera de Sacramento s/n, 04120 Almeria, Spain. FAU - Lopez, Maria Jose AU - Lopez MJ AD - Department of Biology and Geology, CeiA3 and CIAMBITAL, University of Almeria, Carretera de Sacramento s/n, 04120 Almeria, Spain. FAU - Pilar-Cuellar, Fuencisla AU - Pilar-Cuellar F AD - Biomedical Research Networking Center for Mental Health Network (CIBERSAM), Instituto de Salud Carlos III, Santander, Spain; Institute of Biomedicine and Biotechnology of Cantabria (IBBTEC), University of Cantabria-CSIC-SODERCAN, 39011 Santander, Spain; Department of Physiology and Pharmacology, University of Cantabria, 39011 Santander, Spain. FAU - Castro, Elena AU - Castro E AD - Biomedical Research Networking Center for Mental Health Network (CIBERSAM), Instituto de Salud Carlos III, Santander, Spain; Institute of Biomedicine and Biotechnology of Cantabria (IBBTEC), University of Cantabria-CSIC-SODERCAN, 39011 Santander, Spain; Department of Physiology and Pharmacology, University of Cantabria, 39011 Santander, Spain. FAU - Diaz, Alvaro AU - Diaz A AD - Biomedical Research Networking Center for Mental Health Network (CIBERSAM), Instituto de Salud Carlos III, Santander, Spain; Institute of Biomedicine and Biotechnology of Cantabria (IBBTEC), University of Cantabria-CSIC-SODERCAN, 39011 Santander, Spain; Department of Physiology and Pharmacology, University of Cantabria, 39011 Santander, Spain. FAU - Flores, Pilar AU - Flores P AD - Department of Psychology and Health Research Centre, University of Almeria, Carretera de Sacramento s/n, 04120 Almeria, Spain. FAU - Moreno, Margarita AU - Moreno M AD - Department of Psychology and Health Research Centre, University of Almeria, Carretera de Sacramento s/n, 04120 Almeria, Spain. Electronic address: mgmoreno@ual.es. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200813 PL - Netherlands TA - Brain Behav Immun JT - Brain, behavior, and immunity JID - 8800478 RN - 0 (Anti-Bacterial Agents) SB - IM MH - Animals MH - Anti-Bacterial Agents/pharmacology MH - Choice Behavior MH - *Impulsive Behavior MH - Male MH - *Nucleus Accumbens MH - Rats MH - Rats, Wistar MH - Reaction Time OTO - NOTNLM OT - 5-CSRT task OT - Antibiotic treatment OT - Cytokines OT - Delay-discounting task OT - Group A Streptococcus OT - Impulsivity OT - Inhibitory control COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2020/08/18 06:00 MHDA- 2021/04/28 06:00 CRDT- 2020/08/18 06:00 PHST- 2020/01/20 00:00 [received] PHST- 2020/08/04 00:00 [revised] PHST- 2020/08/11 00:00 [accepted] PHST- 2020/08/18 06:00 [pubmed] PHST- 2021/04/28 06:00 [medline] PHST- 2020/08/18 06:00 [entrez] AID - S0889-1591(20)30083-0 [pii] AID - 10.1016/j.bbi.2020.08.010 [doi] PST - ppublish SO - Brain Behav Immun. 2020 Oct;89:675-688. doi: 10.1016/j.bbi.2020.08.010. Epub 2020 Aug 13.