Antidepressant-like activity of S 20098 (agomelatine) in the forced swimming test in rodents: involvement of melatonin and serotonin receptors
Bibliographic record
Abstract
OBJECTIVE: To study agomelatine (S 20098), a potent agonist at melatonin receptors and antagonist at serotonin-2C (5-HT(2C)) receptors, in an animal model of depression, namely, the rodent forced swimming test (FST). METHODS: The effects of acute and repeated administration of S 20098 were compared with those of melatonin (4, 8, 16, 32, 64 mg/kg intraperitoneally [IP] for mice), imipramine (64 mg/kg orally for rats, 8 mg/kg IP for mice) and fluoxetine (16 mg/kg IP for mice). The influence of the pretreatments with 5-HT(1A) or 5-HT(1B) receptor agonists (8-OH-DPAT, anpirtoline) and 5-HT(1A/1B), 5-HT(2A/2C) or 5-HT(3) antagonists (pindolol, ritanserin, ondansetron) on the effects of S 20098 or melatonin were compared with imipramine and fluoxetine in mice. RESULTS: Acute or repeated (13 days) administration of S 20098 or imipramine in rats significantly decreased the duration of immobility during the FST at all doses. A dose-dependent effect was observed after the repeated treatment with S 20098. When given for 10 days to mice in the evening, S 20098 was active on the FST at doses of 4, 16 and 32 mg/kg, whereas the acute administration of S 20098 (in the morning and evening) was without any significant effect. Acute or repeated administration of S 20098 did not modify the locomotor activity of mice. The combination of S 20098 with the above-mentioned pretreatments enhanced the effects of S 20098, given alone, on the duration of immobility. By comparison, acute melatonin was inactive in the FST and only pretreatment with 8-OH-DPAT or pindolol revealed an anti-immobility effect. A pretreatment with 8-OH-DPAT also induced anti-immobility effects with imipramine, but not fluoxetine, whereas pindolol exerted additive effects with fluoxetine but not imipramine. CONCLUSION: These results demonstrate the antidepressant-like activity of repeated administration of S 20098 in the FST. Moreover, the combination of 5-HT agonists and antagonists leads to more powerful effects with S 20098 than with melatonin, thereby emphasizing the contribution of 5-HT receptors to the antidepressant activity of S 20098. Compared with imipramine and fluoxetine, the 5-HT receptor subtypes that may be involved in the antidepressant-like activity of S 20098 are not similar. Indeed, when considering the binding properties of S 20098, the 5-HT(2C) receptor subtype appears to be the most attractive candidate. It is concluded that the antidepressant-like activity of S 20098 in this model most probably involves a combination of both its melatonin agonist and 5-HT(2C )receptor antagonist properties.
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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 | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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".