Dysfunction of serotonergic activity and emotional responses across the light‐dark cycle in mice lacking melatonin MT<sub>2</sub> receptors
Bibliographic record
Abstract
Abstract Melatonin (MLT) levels fluctuate according to the external light/dark cycle in both diurnal and nocturnal mammals. We previously demonstrated that melatonin MT 2 receptor knockout (MT 2 −/− ) mice show a decreased nonrapid eye movement sleep over 24 hours and increased wakefulness during the inactive (light) phase. Here, we investigated the role of MT 2 receptors in physiological light/dark cycle fluctuations in the activity of dorsal raphe nucleus (DRN) serotonin (5‐HT) neurons and anxiety‐ and depression‐like behavior. We found that the 5‐HT burst‐firing activity was tonically reduced across the whole 24 hours in MT 2 −/− mice compared with MT 2 +/+ mice. Importantly, the physiological changes in the spontaneous firing activity of DRN 5‐HT neurons during the light/dark cycle were nullified in MT 2 −/− mice, with a higher DRN 5‐HT neural firing activity during the light phase in MT 2 −/− than in MT 2 +/+ mice. The role of MT 2 receptors over DRN 5‐HT neurons was confirmed by acute pharmacological studies in which the selective MT 2 receptors agonist UCM1014 dose dependently inhibited DRN 5‐HT activity, mostly during the dark phase. Compared with MT 2 +/+ , MT 2 −/− mice displayed an anxiety‐like phenotype in the novelty‐suppressed feeding and in the light/dark box tests; while anxiety levels in the light/dark box test were lower during the dark than during the light phase in MT 2 +/+ mice, the opposite was seen in MT 2 −/− mice. No differences between MT 2 +/+ and MT 2 −/− mice were observed for depression‐like behavior in the forced swim and in the sucrose preference tests. These results suggest that MT 2 receptor genetic inactivation impacts 5‐HT neurotransmission and interferes with anxiety levels by perturbing the physiologic light/dark pattern.
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 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".