TY - JOUR T1 - Corticotropin-Releasing Hormone<sub>1</sub> Receptors Mediate Consensus Interferon-α YM643-Induced Depression-Like Behavior in Mice JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 181 LP - 187 VL - 292 IS - 1 AU - Mayumi Yamano AU - Hidenobu Yuki AU - Syuhei Yasuda AU - Keiji Miyata Y1 - 2000/01/01 UR - http://jpet.aspetjournals.org/content/292/1/181.abstract N2 - 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 × 108–2 × 109 U/kg) and sumiferon (2 × 106–2 × 107I.U./kg) dose-dependently increased immobility time. Repeated s.c. injection of either YM643 (6 × 106–6 × 108 U/kg) or sumiferon (6 × 104–6 × 106 I.U./kg) for 7 days also dose-dependently increased immobility time. After i.c.v. injection of either YM643 (2 × 106 U/mouse) or sumiferon (6 × 104I.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 ID50values 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. The American Society for Pharmacology and Experimental Therapeutics ER -