title: Effects of aspirin on immobile behavior and endocrine and immune changes in the forced swimming test: comparison to fluoxetine and imipramine.
abstract: Aspirin (ASP) is the most commonly used non-steroidal anti-inflammatory drug in the world. Recent clinical and preclinical evidence suggests that ASP may also exert psychoactive effects. It remains unclear whether ASP has antidepressant-like activity, and any molecular mechanisms underlying such activity have yet to be elucidated. Using the forced swimming test (FST), a well-established animal model of depression widely used to screen potential antidepressants in rodents, we investigated the effects of subacute treatment with ASP (0, 6, 12, 25, and 50mg/kg, i.p.) on immobility in the FST, and on FST-induced changes in endocrine and immune parameters in rats, in comparison to the clinical antidepressants imipramine (IMI) and fluoxetine (FLU). Serum levels of corticosterone, pro-inflammatory cytokine interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbent assay. ASP dose-dependently decreased immobility in the FST, without altering the locomotor activity in the open-field test. The inhibitory effects of higher doses (25 and 50mg/kg) of ASP on immobility were similar to that of FLU and IMI at a dose of 10mg/kg. In addition, the levels of corticosterone, IL-6, and TNF-α in peripheral blood were significantly increased after the FST exposure. IMI, but not FLU and ASP at any dose tested, significantly attenuated corticosterone responses in the FST. Both FLU and IMI treatment reduced the increase of IL-6 and TNF-α levels following the FST exposure. ASP dose-dependently decreased FST-induced increase of cytokine levels, as manifested by significantly stronger effects on IL-6 and TNF-α levels at higher doses (25 and 50mg/kg) than the lowest dose of ASP (6 mg/kg). In all, these results indicate that ASP treatment dose-dependently decreased the immobility time and the release of pro-inflammatory cytokines in the FST, suggesting that the anti-inflammatory effects of ASP might be involved in the antidepressant-like effect.
authors.affiliation: The University of Chinese Academy of Sciences, Beijing 100049, China; Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Xi-ting
authors.initials: XT
authors.lastname: Guan
authors.affiliation: Department of Psychology, Peking University, Beijing 100871, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Shao
authors.affiliation: The University of Chinese Academy of Sciences, Beijing 100049, China; Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Xie
authors.affiliation: School of Life Sciences, University of Science and Technology of China, Anhui, 230026, China. Electronic address: linchen@ustc.edu.cn.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: wangww@psych.ac.cn.
authors.forename: Weiwen
authors.initials: W
authors.lastname: Wang
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D003345:Corticosterone / Q000097:blood; D004702:Endocrine Glands / Q000187:drug effects*; D005473:Fluoxetine / Q000494:pharmacology*; D007099:Imipramine / Q000494:pharmacology*; D007107:Immune System / Q000187:drug effects*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013550:Swimming; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000928:Antidepressive Agents; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D005473:Fluoxetine; D007099:Imipramine; D001241:Aspirin; D003345:Corticosterone
keywords: Antidepressant; Aspirin; Corticosterone; Forced swimming test; IL-6; TNF-α