0285 The Effect of Chronic Trazodone Administration on Sleep in the APPNL-F Mouse Model of Alzheimer’s Disease
Bibliographic record
Abstract
Abstract Introduction Sleep disturbances are prevalent among individuals diagnosed with Alzheimer’s disease (AD), typically manifested as low levels of slow-wave sleep (SWS; N3 stage). Restoring SWS has been suggested as an intervention to slow AD progression. Trazodone is a licensed antidepressant also commonly prescribed to manage sleep disturbances due to its hypnotic effects, safety, and tolerability. However, there is limited preclinical research on the effects of trazodone beyond the antidepressant effects. We investigated the effect of voluntary oral trazodone administration at doses 0mg, 10mg, 40mg, and 60 mg/kg on sleep in C57BL/6J mice (n=15; age 10-13 months). We found that a single dose of trazodone hydrochloride (HCL) has a dose-dependent effect on the duration of non-rapid eye movement (NREM) and delta power; 60 mg/kg caused an increase in NREM compared to the baseline (mean increase = 1.54 h ± 0.40 SEM; mixed-design ANOVA dose x vigilance state F(6, 36) = 17.89, p < 0.0001). Methods We then investigated the effect of chronic trazodone administration on sleep in a mouse model of AD (APP NL-F) in a younger (n=16, 9 months-old) and older (n=18, 14 months-old) cohort. Trazodone was administered orally at 60mg/kg through voluntary intake for 60 days. Mice were implanted with EEG/EMG headmounts and were recorded for 7 sessions, each lasting 48 h over the 60-day treatment period. Our results show that the mice reliably consumed trazodone throughout the treatment period, with n=30/34 mice fully consuming the trazodone on all 60 days. The EEG/EMG data were manually scored for wake, NREM, and rapid eye movement (REM). Results Preliminary analysis for 9 months-old cohort showed a significant effect of treatment on NREM sleep (repeated measures ANOVA, F(4, 12) = 21.433, p < 0.001). Post hoc analysis confirmed increased NREM sleep after 60 days, compared to the baseline (p = 0.0205). Conclusion Together, these studies demonstrate for the first time that trazodone dose-dependently increases SWS in mice and that trazodone can enhance NREM sleep in a mouse model of AD, even after 60 days of treatment. Support (if any) This Work was funded by NSERC Discovery Grant (RGPIN/03909-2021, BAK), CRC (CRC-2020-00047, BAK), and CFI (CFI-41428, BAK).
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".