title: Antibiotic treatment attenuates behavioral and neurochemical changes induced by exposure of rats to group a streptococcal antigen.
abstract: Post-streptococcal A (GAS) sequelae including movement and neuropsychiatric disorders have been associated with improvement in response to antibiotic therapy. Besides eradication of infection, the underlying basis of attenuation of neuropsychiatric symptoms following antibiotic treatment is not known. The aim of the present study was to test the efficacy of antibiotic treatment in a rat model of GAS-related neuropsychiatric disorders. In the model, rats were not infected but were exposed to GAS-antigen or to adjuvants only (Control rats) and treated continuously with the antibiotic ampicillin in their drinking water from the first day of GAS-antigen exposure. Two additional groups of rats (GAS and Control) did not receive ampicillin in their drinking water. Behavior of the four groups was assessed in the forced swim, marble burying and food manipulation assays. We assessed levels of D1 and D2 dopamine receptors and tyrosine hydroxylase in the prefrontal cortex and striatum, and IgG deposition in the prefrontal cortex, striatum and thalamus. Ampicillin treatment prevented emergence of the motor and some of the behavioral alterations induced by GAS-antigen exposure, reduced IgG deposition in the thalamus of GAS-exposed rats, and tended to attenuate the increase in the level of TH and D1 and D2 receptors in their striatum, without concomitantly reducing the level of sera anti-GAS antibodies. Our results reinforce the link between exposure to GAS antigen, dysfunction of central dopaminergic pathways and motor and behavioral alterations. Our data further show that some of these deleterious effects can be attenuated by antibiotic treatment, and supports the latter's possible efficacy as a prophylactic treatment in GAS-related neuropsychiatric disorders.
authors: School of Psychological Sciences and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
authors: Dafna
authors: D
authors: Lotan
authors: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
authors: Madeleine
authors: M
authors: Cunningham
authors: School of Psychological Sciences and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
authors: Daphna
authors: D
authors: Joel
mesh_terms: D000667:Ampicillin / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000942:Antigens, Bacterial / Q000276:immunology*; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D011917:Rats, Inbred Lew; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D013290:Streptococcal Infections / Q000188:drug therapy* / Q000276:immunology* / Q000382:microbiology; D013297:Streptococcus pyogenes / Q000276:immunology*; D013550:Swimming; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D000942:Antigens, Bacterial; D007074:Immunoglobulin G; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D000667:Ampicillin; D014446:Tyrosine 3-Monooxygenase