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We recently showed that reactivation of chronic<jats:named-content content-type=\"genus-species\">T. gondii<\/jats:named-content>infection induced depression-like behaviors in mice. Furthermore, it has been hypothesized that depression-like behaviors are mediated via a host defense mechanism against invading pathogens; proximate mechanisms of this behavioral hypothesis remain unclear. In the present study, we investigate the contribution of indoleamine 2,3-dioxygenase (IDO), inflammation, and interferon gamma (IFN-\u03b3) to anhedonic and despair-related behaviors in<jats:named-content content-type=\"genus-species\">T. gondii<\/jats:named-content>-infected mice by using sucrose preference and forced-swim tests, respectively. First, we confirmed that BALB\/c mice exhibited both sickness and depression-like behaviors during acute infection. Treatment of infected wild-type mice with minocycline (anti-inflammatory drug) abated sickness and anhedonic and despair-like behaviors, whereas in<jats:named-content content-type=\"genus-species\">T. gondii<\/jats:named-content>-infected mice, treatment normalized kynurenine\/tryptophan (Kyn\/Trp) ratios in both plasma and brain tissue. Additionally,<jats:named-content content-type=\"genus-species\">T. gondii<\/jats:named-content>infection failed to induce anhedonic and despair-like behaviors or increase the Kyn\/Trp ratio in immunocompromised (IFN-\u03b3<jats:sup>\u2212\/\u2212<\/jats:sup>) mice, whereas sickness behavior was observed in both immunocompetent and IFN-\u03b3<jats:sup>\u2212\/\u2212<\/jats:sup>mice following infection. Furthermore, treatment with 1-methyl tryptophan (an IDO inhibitor) did not affect locomotor activity, attenuated clinical scores and anhedonic and despair-like behaviors, and resulted in normal Kyn\/Trp ratios in<jats:named-content content-type=\"genus-species\">T. gondii<\/jats:named-content>-infected wild-type mice. Although low levels of serotonin and dopamine were observed in the brain during acute and chronic infections, anhedonic and despair-like behaviors were not detected in the chronic stage of infection. Collectively, our results demonstrated that immune enhancement in response to infection with<jats:named-content content-type=\"genus-species\">T. gondii<\/jats:named-content>resulted in IFN-\u03b3 production, IDO activation, and inflammation associated with anhedonic and despair-like behaviors.<\/jats:p>","DOI":"10.1128\/iai.00007-17","type":"journal-article","created":{"date-parts":[[2017,1,31]],"date-time":"2017-01-31T02:20:26Z","timestamp":1485829226000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":27,"title":["Involvement of Host Defense Mechanisms against Toxoplasma gondii Infection in Anhedonic and Despair-Like Behaviors in Mice"],"prefix":"10.1128","volume":"85","author":[{"given":"Motamed Elsayed","family":"Mahmoud","sequence":"first","affiliation":[{"name":"National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido, Japan"},{"name":"Department of Animal Behavior, Management, Genetics and Breeding, Faculty of Veterinary Medicine, Sohag University, Sohag, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ragab","family":"Fereig","sequence":"additional","affiliation":[{"name":"National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshifumi","family":"Nishikawa","sequence":"additional","affiliation":[{"name":"National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/archgenpsychiatry.2012.668"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.11m07532"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2015.11.005"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3128869"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2006.09.006"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4001119"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2012.2"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4002148"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2008.04.001"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0889-1591(02)00014-4"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2013.04.003"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4001600"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.PSY.0000078188.74020.CC"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1991.tb03460.x"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.26.15769"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.23.13496"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2297"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1994.tb24733.x"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.24.14014"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir621"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1073514"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(02)00176-5"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1107"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2012.04.022"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-11-41"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-0135-0_19"},{"key":"e_1_3_3_28_2","first-page":"611","article-title":"Dramatic changes in oxidative tryptophan metabolism along the kynurenine pathway in experimental cerebral and noncerebral malaria","volume":"152","author":"Sanni LA","year":"1998","unstructured":"Sanni LA Thomas SR Tattam BN Moore DE Chaudhri G Stocker R Hunt NH . 1998. 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