Enhancement of immobility in mouse forced swimming test by treatment with human interferon.
We investigated the depression induced by human interferons using the forced swimming test in mice. Intravenous (i.v.) administration of interferon-alpha s (natural interferon-alpha, recombinant interferon-alpha-2a and recombinant interferon-alpha-2b, 600-60000 IU/kg) increased the immobility time in the forced swimming test in a dose-dependent manner, but natural interferon-beta and recombinant interferon-gamma-1a did not affect the immobility time. The increase in the immobility time induced by recombinant interferon-alpha-2b peaked at 15 min after dosing. Administration of recombinant interferon-alpha-2b (6000 IU/kg, i.v.) once daily for 7 consecutive days increased the immobility time, but natural interferon-beta and recombinant interferon-gamma-la did not. Recombinant interferon-alpha-2b in combination with the anti-depressants imipramine (10 mg/kg, i.p.) and mianserin (20 mg/kg, i.p.) did not increase the immobility time. These results suggest that interferon-alpha has a greater potential for inducing depression than interferon-beta and -gamma, and that anti-depressants are effective against interferon-alpha-induced depression.
Drug Safety Research Laboratory, Daiichi Pharmaceutical, Tokyo, Japan.
M
M
Makino
Y
Y
Kitano
M
M
Hirohashi
K
K
Takasuna
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007099:Imipramine / Q000494:pharmacology; D007275:Injections, Intravenous; D016898:Interferon-alpha / Q000494:pharmacology; D007372:Interferons / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D013550:Swimming; D013997:Time Factors
D000929:Antidepressive Agents, Tricyclic; D000998:Antiviral Agents; D016898:Interferon-alpha; D007372:Interferons; D007099:Imipramine