Involvement of central opioid systems in human interferon‐α induced immobility in the mouse forced swimming test

We investigated the mechanism by which human interferon‐α (IFN‐α) increases the immobility time in a forced swimming test, an animal model of depression. Central administration of IFN‐α (0.05–50 IU per mouse, i.cist.) increased the immobility time in the forced swimming test in mice in a dose‐dependent manner. Neither IFN‐β nor ‐γ possessed any effect under the same experimental conditions. Pre‐treatment with an opioid receptor antagonist, naloxone (1 mg kg −1 , s.c.) inhibited the prolonged immobility time induced by IFN‐α (60 KIU kg −1 , i.v. or 50 IU per mouse. i.cist.). 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‐α, while intracisternal administration of naloxone methiodide (1 nmol per mouse) completely blocked. The effect of IFN‐α was inhibited by a μ 1 ‐specific opioid receptor antagonist, naloxonazine (35 mg kg −1 , s.c.) and a μ 1 /μ 2 receptor antagonist, β‐FNA (40 mg kg −1 , s.c.). A selective δ‐opioid receptor antagonist, naltrindole (3 mg kg −1 , s.c.) and a κ‐opioid receptor antagonist, nor‐binaltorphimine (20 mg kg −1 , s.c.), both failed to inhibit the increasing effect of IFN‐α. These results suggest that the activator of the central opioid receptors of the μ 1 ‐subtype might be related to the prolonged immobility time of IFN‐α, but δ and κ‐opioid receptors most likely are not involved.British Journal of Pharmacology (2000) 130 , 1269–1274; doi: 10.1038/sj.bjp.0703432