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Effects of chronic trazodone administration on cognitive performance in the APPNL-F mouse model of Alzheimer's disease

Poster Session C - Sunday, March 8, 2026, 5:00 – 7:00 pm PDT, Fairview/Kitsilano Ballroom

Robert Gibson^1,2 (), Taha Yildirim^1,2, Hillary Han¹, Kiana Shakiba¹, Artemis Kohanfekr¹, Sofiya Soboleva¹, Daniela Purvica¹, Sarah McGuire¹, Dana Braynina¹, Jefferey Yue^1,2, Mayuko Arai^1,3, Brianne Kent^1,2; ¹Simon Fraser University, ²Institute for Neuroscience and Neurotechnology, ³University of California, Davis

Sleep disturbances are prevalent among individuals diagnosed with Alzheimer’s disease (AD) and sleep is being explored as a therapeutic target for AD. The current study aims to assess the effects of trazodone, an antidepressant with sleep-promoting properties, on cognition in a mouse model of AD. We previously developed a voluntary oral administration paradigm to administer trazodone hydrochloride (60mg/kg) to mice. Using our protocol, we demonstrated that trazodone increased slow wave sleep in the APPNL-F mice and reduced amyloid plaque neuropathology. Here, we administered trazodone to 14-month-old APPNL-F mice (N = 16, treatment = 8, female = 8) for 120 days. Cognitive performance was assessed using touchscreen cognitive testing (Bussey-Saksida, Lafayette Instruments; Paired Associates Learning (dPAL) and Location Discrimination (LD) tasks) and novel object recognition. Trazodone treated mice demonstrated a higher accuracy on LD Punish Incorrect (p = 0.011) and exhibited a higher preference for novel objects after a 1h delay (p = 0.006). Further cognitive testing and neuropathology assessment is ongoing. Our results suggest that trazodone should be explored as a potential disease-modifying therapeutic for AD, with potential beneficial effects on cognition and neuropathology.

Topic Area: LONG-TERM MEMORY: Development & aging