IMMUNOSUPPRESSIVE TREATMENT PREVENTS BEHAVIORAL DEFICIT IN AUTOIMMUNEMRL-LPR MICE

MRL-lpr mice, which develop severe autoimmune disease, explore novel o bjects less well than do their congenic MRL-+/+ controls, in which sym ptoms of the disease are relatively mild. Moreover, diminished explora tion in MRL-lpr mice correlates with the elevated titers of antinuclea r antibodies (ANA) in their sera, suggesting that this behavioral defi cit is caused by the autoimmune process. To test the hypothesis that a utoimmunity affects behavior, in this study we examine whether treatme nt of the autoimmune process will reduce the difference in performance between the two MRL substrains in the novel-object test. Forty mice i n each substrain were treated from 4 to 10 wk of age with the immunosu ppressive drug, cyclophosphamide (100 mg/kg/wk, IP) or a saline vehicl e. The immunosuppressive treatment reduced ANA titers to low levels an d eliminated ANA production completely in 55% of MRL-lpr mice, suggest ing an attenuation of the autoimmune process. In addition, treatment w ith cyclophosphamide, but not saline, abolished significant difference s in exploration between the MRL-lpr and MRL +/+ groups, as measured b y the latency to touch a novel object and the time spent exploring it. Thus, the present results suggest that a treatment which ameliorates autoimmune symptoms can concurrently remove the substrain difference i n behavior. The effect of cyclophosphamide in the MRL-lpr group is bel ieved to reflect the suppression of pathogenic immune factor(s) that a lter behavior during the onset of autoimmune disease.