Behavioral effects of infection with interferon-gamma adenovector.
Anxiety and depression of unknown etiology are frequent complications of the systemic autoimmune disease lupus erythematosus (SLE). To elucidate key pathogenic factors we study the "autoimmunity-associated behavioral syndrome" (AABS) in lupus-prone MRL-lpr mice. Based on the evidence that serum levels of the neuroactive cytokine interferon-gamma (IFN-gamma) are increased both in human and murine forms of SLE, the present study examines whether sustained IFN-gamma production in non-autoimmune mice induces deficits comparable to AABS, particularly in tasks reflective of emotional reactivity and motivated behavior. For this purpose, wild-type and IFN-gamma knockout C57BL/6J mice were infected with adenovirus carrying the cDNA for murine IFN-gamma (i.p. 2 x 10(8) pfu of virus per mouse) and shortly thereafter tested in the behavioral battery used in the detection of AABS. Serum levels of IFN-gamma were found to peak 24 h after the infection, normalized within 5 days. Although all infected animals showed reduced food/water intake and body weight, the recovery rate was slower in groups injected with IFN-gamma virus. No deficits were observed in the models of anxiety, but blunted responsiveness in the sucrose preference test (a putative model of anhedonia) lasted well beyond the IFN-gamma clearance period. These results suggest that a relatively brief elevation in systemic IFN-gamma levels impairs ingestive behavior and leads to prolonged changes in motivated behavior. As such, they are consistent with the hypothesis that upregulation in synthesis of pro-inflammatory cytokines contributes to induction of AABS and more specifically, to limbic system dysfunction during lupus-like disease.
Kwant
Amanda
A
Department of Psychiatry and Behavioral Neurosciences, McMaster University, HSC Rm 4N81, 1200 Main St. West, Hamilton, Ont., Canada L8N 3Z5.
Sakic
Boris
B
D000256:Adenoviridae / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D001835:Body Weight / Q000187:drug effects / Q000276:immunology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004326:Drinking / Q000187:drug effects / Q000276:immunology; D004435:Eating / Q000187:drug effects / Q000276:immunology; D005518:Food Preferences / Q000187:drug effects; D005822:Genetic Vectors; D007371:Interferon-gamma / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013550:Swimming; D013997:Time Factors; D014162:Transfection
D007371:Interferon-gamma