Development of a murine animal model of depression for repeated dosing with human interferon alpha

Neuropsychiatric adverse effects of interferon (IFN) alpha are well known. There is little clinically relevant research on animal models of depression with recombinant human IFN alpha 2b (rhIFN-α2b).

To identify an appropriate dose and duration of administration of recombinant human interferon alpha-2b (rhIFN-α2b) to establish a convenient and clinically relevant murine model of chronic rhIFN-α2b-induced depression using the forced swim test (FST).

Using a 4×3 factorial design, rhIFN-α2b was administered subcutaneously to mice (n=180) in the dose range of 400, 800, and 1600 IU/g/day for 5, 10, and 15 days; saline-treated mice formed the control groups. In each group, 1 day after the last dose, the mice were assessed for immobility in the FST. In another experiment, at these same doses and time points, the effect of rhIFN-α2b on murine motility was assessed in the small open field.

We found that rhIFN-α2b significantly increased immobility in the FST. The immobility was detectable by day 5 and did not increase with duration of IFN treatment. The immobility was apparent with the 400 IU/g/day dose and was not greater at higher IFN doses. At no dose or time point did rhIFN-α2b alter murine motility in the small open field.

We conclude that rhIFN-α2b-induced behavioral despair, represented by immobility in the FST, is not due to reduced basal motility. The FST may therefore be used as a convenient Swiss albino mouse model of chronic rhIFN-α2b-induced depression with a 400-1600 IU/g/day dose administered subcutaneously for 5-15 days. The most economical model is 400 IU/g/day administered for 5 days.