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Br J Pharmacol. 2000 Jul;130(6):1269-74.

Involvement of central opioid systems in human interferon-alpha induced immobility in the mouse forced swimming test.

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  • 1Drug Safety Research Laboratory, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.


1. We investigated the mechanism by which human interferon-alpha (IFN-alpha) increases the immobility time in a forced swimming test, an animal model of depression. 2. Central administration of IFN-alpha (0.05 - 50 IU per mouse, i.cist.) increased the immobility time in the forced swimming test in mice in a dose-dependent manner. 3. Neither IFN-beta nor -gamma possessed any effect under the same experimental conditions. 4. Pre-treatment with an opioid receptor antagonist, naloxone (1 mg kg(-1), s.c.) inhibited the prolonged immobility time induced by IFN-alpha (60 KIU kg(-1), i.v. or 50 IU per mouse. i.cist. ). 5. Peripheral administration of naloxone methiodide (1 mg kg(-1), s. c.), which does not pass the blood - brain barrier, failed to block the effect of IFN-alpha, while intracisternal administration of naloxone methiodide (1 nmol per mouse) completely blocked. 6. The effect of IFN-alpha was inhibited by a mu(1)-specific opioid receptor antagonist, naloxonazine (35 mg kg(-1), s.c.) and a mu(1)/mu(2) receptor antagonist, beta-FNA (40 mg kg(-1), s.c.). A selective delta-opioid receptor antagonist, naltrindole (3 mg kg(-1), s.c.) and a kappa-opioid receptor antagonist, nor-binaltorphimine (20 mg kg(-1), s.c.), both failed to inhibit the increasing effect of IFN-alpha. 7. These results suggest that the activator of the central opioid receptors of the mu(1)-subtype might be related to the prolonged immobility time of IFN-alpha, but delta and kappa-opioid receptors most likely are not involved.

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