Antidepressant-like activity of S 20098 (agomelatine) in the forced swimming test in rodents: involvement of melatonin and serotonin receptors
by
Bourin M, Mocaer E, Porsolt R.
Bourin - EA 3256, Neurobiologie de l'anxiete et de la depression,
Faculte de Medecine, Nantes, France,
and
Neurochemical Research Unit, Department of Psychiatry,
University of Alberta, Edmonton, Alta.;
Mocaer - Institut de Recherches Internationales Servier, Courbevoie, France;
Porsolt - Porsolt and Partners Pharmacology, Boulogne-Billancourt, France.
J Psychiatry Neurosci. 2004 Mar;29(2):126-133


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.
5-HT2c
Valdoxan
Serotonin
Dopamine
Melatonin
SB-243213
Agomelatine
Agomelatine: structure
Agomelatine (Valdoxan): review
Agomelatine, stress and memory
New antidepressants: agomelatine
Agomelatine (Valdoxan) and melatonergic drugs
Agomelatine (Valdoxan): efficacy and tolerance profile
Agomelatine, 5-HT2c antagonist and melatonin agonist
Agomelatine and new nerve cell growth in the hippocampus
Agomelatine in the treatment of seasonal affective disorder (SAD)
Agomelatine (Valdoxan, Melitor, Thymanax) to treat major depression
Agomelatine (Valdoxan) and the serotonin 5-HT2b and 5-HT2c receptors
Pathophysiology of depression: Role of sleep and the melatonergic system
Jet lag: therapeutic use of melatonin and possible application of melatonin analogs


Refs
and further reading

HOME
HedWeb
Nootropics
cocaine.wiki
Future Opioids
BLTC Research
MDMA/Ecstasy
Superhapiness?
Utopian Surgery?
The Abolitionist Project
The Hedonistic Imperative
The Reproductive Revolution
Critique of Huxley's Brave New World

The Good Drug Guide
The Good Drug Guide

The Responsible Parent's Guide
To Healthy Mood Boosters For All The Family