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Antidepressant-like activity of S 20098 (agomelatine) in the forced swimming test in rodents: involvement of melatonin and serotonin receptors.
J Psychiatry Neurosci. 2004 Mar; 29(2):126-33.JP

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.

Authors+Show Affiliations

EA 3256, Neurobiologie de l'anxiété et de la dépression, Faculté de Médecine, Nantes, France. mbourin@sante.univ-nantes.frNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15069466

Citation

Bourin, Michel, et al. "Antidepressant-like Activity of S 20098 (agomelatine) in the Forced Swimming Test in Rodents: Involvement of Melatonin and Serotonin Receptors." Journal of Psychiatry & Neuroscience : JPN, vol. 29, no. 2, 2004, pp. 126-33.
Bourin M, Mocaër E, Porsolt R. Antidepressant-like activity of S 20098 (agomelatine) in the forced swimming test in rodents: involvement of melatonin and serotonin receptors. J Psychiatry Neurosci. 2004;29(2):126-33.
Bourin, M., Mocaër, E., & Porsolt, R. (2004). Antidepressant-like activity of S 20098 (agomelatine) in the forced swimming test in rodents: involvement of melatonin and serotonin receptors. Journal of Psychiatry & Neuroscience : JPN, 29(2), 126-33.
Bourin M, Mocaër E, Porsolt R. Antidepressant-like Activity of S 20098 (agomelatine) in the Forced Swimming Test in Rodents: Involvement of Melatonin and Serotonin Receptors. J Psychiatry Neurosci. 2004;29(2):126-33. PubMed PMID: 15069466.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antidepressant-like activity of S 20098 (agomelatine) in the forced swimming test in rodents: involvement of melatonin and serotonin receptors. AU - Bourin,Michel, AU - Mocaër,Elisabeth, AU - Porsolt,Roger, PY - 2004/4/8/pubmed PY - 2004/5/18/medline PY - 2004/4/8/entrez SP - 126 EP - 33 JF - Journal of psychiatry & neuroscience : JPN JO - J Psychiatry Neurosci VL - 29 IS - 2 N2 - 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. SN - 1180-4882 UR - https://www.unboundmedicine.com/medline/citation/15069466/Antidepressant_like_activity_of_S_20098__agomelatine__in_the_forced_swimming_test_in_rodents:_involvement_of_melatonin_and_serotonin_receptors_ L2 - http://www.jpn.ca/vol29-issue2/29-2-126/ DB - PRIME DP - Unbound Medicine ER -