Role of IL-1 in poststroke depressive-like behavior in mice

Background. Poststroke depression (PSD) leads to impaired functional recovery and increased mortality, yet physiological mechanisms are unknown. The present study investigates the roles of glucocorticoids and interleukin-1 (IL-1) in poststroke anhedonia. Methods: Adult male mice underwent middle cerebral artery occlusion (MCAO), and were recovered 7 days. Mice were treated with metyrapone (100 mg/kg intraperitoneally), mifepristone (50 mg/kg subcutaneously), or vehicle injections on reperfusion days 4-7. A separate cohort of mice was implanted with cannulae and was administered IL-1 receptor antagonist (IL-1ra) or vehicle (6 mu g intracerebroventricularly) on reperfusion days 6 and 7. After the final injection or infusion, sucrose consumption was recorded for 6 hours. Results. Mice in the sham-treated group consumed significantly more sucrose solution than water, whereas MCAO-treated mice consumed similar amounts of each, suggesting anhedonia among MCAO-treated mice. A separate experiment assessed whether stroke-induced increases in corticosteroids or IL-1 contribute to anhedonia. Only IL-1ra restored sucrose consumption in MCAO-treated mice. Vehicle-MCAO-treated mice drank significantly less sucrose solution than did both IL-1ra and vehicle-sham treatment groups, whereas IL-1ra-MCAO-treated mice drank similar amounts to both sham-treated groups. Conclusions: Poststroke anhedonia, a symptom of depression in human beings, can be reproduced in a mouse model of stroke and appears to involve altered IL-1 transmission in the brain.