S01-01 - 5-HT<sub>4</sub> Agonists: a Putative New Class of Antidepressants, with a Faster Onset of Action
Bibliographic record
Abstract
Objectives Current antidepressants are clinically effective only after several weeks of administration. Because our previous studies indicated that both acute and sustained stimulation of serotonin4 (5-HT4) receptors facilitate central 5-HT activity, we assessed the ability of 5-HT4 agonists to induce antidepressant-like effects in the rat brain within a short (3 days) time-frame. Methods and results We found that 5-HT4 agonists reduce immobility in the Forced Swimming Test, displaying an antidepressant potential. Moreover, a 3-day regimen with such compounds modify rat brain parameters considered as key markers of antidepressant action, but observed only after 2-3 week treatments with classical molecules: desensitization of 5-HT1A autoreceptors, increased tonus on hippocampal postsynaptic 5-HT1A receptors, enhanced phosphorylation of the CREB protein and neurogenesis in the hippocampus. A 3-day regimen with the 5-HT4 agonist RS 67333 was also sufficient to reduce both the hyperlocomotion induced by olfactory bulbectomy, and the diminution of sucrose intake consecutive to a chronic mild stress. Moreover, the concomitant administration of a 5-HT4 receptor agonists with a classical antidepressant (SSRI) potentiated the amplitude of these effects, without altering the rapidity of action of the former. Conclusions These findings point out 5-HT4 receptor agonists as a putative new class of antidepressants, with a rapid onset of action.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".