Decreased immobility in swimming test by homologous interferon-alpha in mice accompanied with increased cerebral tryptophan level and serotonin turnover.
Animal models are used to decipher the pathophysiology of IFN-alpha-induced psychiatric complications in humans. However, the behavioral effects of IFN-alpha in rodents remain highly controversial. In contrast to homologous IFN-alpha, our recent study revealed that human IFN-alpha, which was used in many previous investigations, had no biological activity in mice. To evaluate the behavioral effects of homologous IFN-alpha in mice, adult C57BL/6J mice were treated with carrier-free murine IFN-alpha and tested on a number of behavioral paradigms. Surprisingly, contrary to previous reports, IFN-alpha treatment decreased the time spent immobile in the forced-swimming test after a single intraperitoneal injection at 2 x 10(6)IU/kg, whereas general locomotor activity was not altered. The elevated plus-maze (EPM) test showed a trend toward an increased anxiety profile in IFN-alpha-treated mice. The tail-suspension and light dark exploration test revealed no difference between IFN-alpha-treated and control animals. Interestingly, neurochemical analysis revealed significantly increased concentrations of tryptophan and 5-hydroxyindoleacetic acid (5-HIAA)/serotonin (5-HT) ratios following IFN-alpha treatment in selected brain regions. Thus, systemic murine IFN-alpha treatment increases swimming time in mice. Increased cerebral serotonin turnover as well as increased tryptophan concentrations, induced by IFN-alpha, implicates serotonergic neurotransmission in behavioral dysfunction caused by this innate immune mediator.
Wang
Jianping
J
Department of Pharmacology & Toxicology, University of Missouri-Kansas City School of Pharmacy, Kansas City, MO 64108, United States. wangjp@umkc.edu
Dunn
Adrian J
AJ
Roberts
Amanda J
AJ
Zhang
Hua
H
D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology; D001008:Anxiety Disorders / Q000139:chemically induced* / Q000276:immunology / Q000503:physiopathology; D001921:Brain / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects / Q000276:immunology; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D055809:Illness Behavior / Q000187:drug effects* / Q000502:physiology; D016898:Interferon-alpha / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects / Q000276:immunology; D009068:Movement / Q000187:drug effects / Q000502:physiology; D009483:Neuropsychological Tests; D012701:Serotonin / Q000378:metabolism*; D014364:Tryptophan / Q000378:metabolism*
D016898:Interferon-alpha; D012701:Serotonin; D014364:Tryptophan