Celecoxib, ibuprofen, and indomethacin alleviate depression-like behavior induced by interferon-alfa in mice

Abstract

Background Interferon-α (IFNα) therapy causes psychiatric side effects, including depression that may result in poor compliance of therapy. It is important to find alternative therapies for the prevention of IFNα induced depression. Non-steroidal anti-inflammatory drugs (NSAIDs) have been useful in depressive disorder. Therefore the effects of celecoxib, ibuprofen, and indomethacin were evaluated following IFNα-induced depression in mice. Methods Male albino mice weighing 26 ± 2 g were used. Depression was induced by IFNα (16 × 105 IU/kg, SC) for six consecutive days. Animals were first subject to the locomotor test, then the splash test and finally the forced swimming test (FST) on the 7th day. The NSAIDs were administered (IP) either one single dose before the test, or simultaneously with IFNα. Results locomotor activity was only impaired by ibuprofen high dose (75 mg/kg), thus it was not further evaluated. Following IFNα therapy depression-like behaviors were observed; significant changes during the splash test (grooming time 24 ± 7 sec vs. control 63 ± 7 sec), the FST (immobility time 166 ± 15 sec vs. control 128 ± 6 sec), and sucrose preference reduced to 64 ± 0.8%. The NSAIDs noticeably reduced the immobility time in FST, while grooming time was increased. Celecoxib and indomethacin single doses were effective while ibuprofen showed better antidepressant effects when it was administered along with IFNα. Conclusions The NSAIDs were able to prevent IFNα induced depression in mice. NSAIDs administration with IFNα does not interfere with clinical benefit effects of IFNα and they could also be useful to prevent IFNα psychiatric side effects, thus further clinical trials are suggested.