Corticotropin-Releasing Hormone1 Receptors Mediate Consensus Interferon-α YM643-Induced Depression-Like Behavior in Mice

Depression-like behavior induced by YM643, a consensus interferon-α (IFN-α), was evaluated with the tail-suspension test in mice and compared with depression-like behavior induced by sumiferon, a natural IFN-α. To investigate the mechanism of IFN-α-induced depression-like behavior, the effects of the tricyclic antidepressant imipramine, the cyclooxygenase inhibitor indomethacin, the opioid receptor antagonist naloxone, and the selective corticotropin-releasing hormone receptor antagonist CP-154,526 on IFN-α-induced depression-like behavior were evaluated. Intravenously injected YM643 (2 × 10 8 –2 × 10 9 U/kg) and sumiferon (2 × 10 6 –2 × 10 7 I.U./kg) dose-dependently increased immobility time. Repeated s.c. injection of either YM643 (6 × 10 6 –6 × 10 8 U/kg) or sumiferon (6 × 10 4 –6 × 10 6 I.U./kg) for 7 days also dose-dependently increased immobility time. After i.c.v. injection of either YM643 (2 × 10 6 U/mouse) or sumiferon (6 × 10 4 I.U./mouse), significant prolongation of immobility time also was observed. Pretreatment with imipramine (30 mg/kg s.c.) significantly reduced the YM643- or sumiferon-induced increases in immobility time. CP-154,526 (0.3–3 mg/kg s.c.) dose-dependently reduced YM643- or sumiferon-induced increases in immobility time with ID 50 values of 0.6 mg/kg against YM643 and 1.3 mg/kg against sumiferon. However, neither indomethacin (10 mg/kg s.c.) nor naloxone (3 mg/kg s.c.) had any effect on YM643- or sumiferon-induced increases in immobility time. These results suggest that IFN-α centrally induces depression-like behavior in mice that can be alleviated with imipramine. The results also suggest that activation of corticotropin-releasing hormone receptors is involved in IFN-α-induced depression-like behavior, but the prostaglandin and opioid systems do not participate in this process.