Decreased immobility in swimming test by homologous interferon-α in mice accompanied with increased cerebral tryptophan level and serotonin turnover

Animal models are used to decipher the pathophysiology of IFN-α-induced psychiatric complications in humans. However, the behavioral effects of IFN-α in rodents remain highly controversial. In contrast to homologous IFN-α, our recent study revealed that human IFN-α, which was used in many previous investigations, had no biological activity in mice. To evaluate the behavioral effects of homologous IFN-α in mice, adult C57BL/6J mice were treated with carrier-free murine IFN-α and tested on a number of behavioral paradigms. Surprisingly, contrary to previous reports, IFN-α treatment decreased the time spent immobile in the forced-swimming test after a single intraperitoneal injection at 2 × 106 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-α-treated mice. The tail-suspension and light dark exploration test revealed no difference between IFN-α-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-α treatment in selected brain regions. Thus, systemic murine IFN-α treatment increases swimming time in mice. Increased cerebral serotonin turnover as well as increased tryptophan concentrations, induced by IFN-α, implicates serotonergic neurotransmission in behavioral dysfunction caused by this innate immune mediator.