Human interferon-alpha induces immobility in the mouse forced swimming test: involvement of the opioid system.
In a previous study, we indicated that human interferon (IFN)-alpha (IFN-alpha, 6 x 10(4) IU/kg, i.v.), but not human IFN-beta or -gamma, prolonged the immobility time of the forced swimming test in mice. In this study, we investigated the mechanism of the effect of human IFN-alpha. None of the mouse IFNs tested (IFN-alpha/beta, IFN-beta, and IFN-gamma, 3 x 10(5) U/kg, i.v.) changed the immobility time or the spontaneous locomotor activity in mice. Indomethacin (10 mg/kg, s.c.), a cyclooxygenase inhibitor, did not affect the increase in the immobility time induced by human IFN-alpha (6 x 10(4) IU/kg, i.v.). However, naloxone (1 mg/kg, s.c.), an opioid receptor antagonist, blocked the increasing caused by human IFN-alpha in the forced swimming test. These results suggest that the increase in the immobility time caused by human IFN-alpha in the forced swimming test might be mediated through opioid receptors, but not mouse IFN receptors.
Makino
M
M
Drug Safety Research Laboratory, Daiichi Pharmaceutical, Tokyo, Japan. makinald@daiichipharm.co.jp
Kitano
Y
Y
Komiyama
C
C
Hirohashi
M
M
Kohno
M
M
Moriyama
M
M
Takasuna
K
K
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D016898:Interferon-alpha / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D018847:Opioid Peptides / Q000502:physiology*; D011930:Reaction Time / Q000187:drug effects; D017471:Receptors, Interferon / Q000502:physiology; D013045:Species Specificity; D013550:Swimming
D016861:Cyclooxygenase Inhibitors; D016898:Interferon-alpha; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D017471:Receptors, Interferon; D009270:Naloxone; D016899:Interferon-beta; D007371:Interferon-gamma; D007213:Indomethacin