Involvement of 5-HT(2C) receptors in the anti-immobility effects of antidepressants in the forced swimming test in mice

Several recent studies have demonstrated that 5-HT(1A), 5-HT(1B) and 5-HT(3) receptors were implicated in the mechanism of action of antidepressants in the mouse forced swimming test. Despite extensive evidence for a role of 5-HT(2C) receptors in depression, the precise role of these receptors in th...

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Bibliographic Details
Published in:European neuropsychopharmacology 2001-04, Vol.11 (2), p.145
Main Authors: Clenet, F, De Vos, A, Bourin, M
Format: Article
Language:English
Subjects:
Animals
Antidepressive Agents - pharmacology
Antidepressive Agents, Tricyclic - pharmacology
Dose-Response Relationship, Drug
Drug Interactions
Ethylamines - pharmacology
Indoles - pharmacology
Male
Mice
Motor Activity - drug effects
Receptor, Serotonin, 5-HT2C
Receptors, Serotonin - drug effects
Serotonin Receptor Agonists - pharmacology
Serotonin Uptake Inhibitors - pharmacology
Swimming - physiology
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Summary:Several recent studies have demonstrated that 5-HT(1A), 5-HT(1B) and 5-HT(3) receptors were implicated in the mechanism of action of antidepressants in the mouse forced swimming test. Despite extensive evidence for a role of 5-HT(2C) receptors in depression, the precise role of these receptors in the effects of clinically established antidepressants was not directly investigated in the mouse forced swimming test. This work was aimed at exploring interactions between several doses of Ro 60-0175, a recently available, full and selective 5-HT(2C) agonist, and antidepressant drugs in the mouse forced swimming test. Spontaneous locomotor activity was measured as an index of intact sensorimotor functions and the dose-effect of Ro 60-0175 alone, as well as interactions with several antidepressants, such as tricyclic antidepressants (imipramine, desipramine and maprotiline) and selective serotonin reuptake inhibitors (paroxetine, citalopram, fluoxetine, fluvoxamine and sertraline), were studied in the mouse forced swimming test. There was no intrinsic antidepressant-like effect of Ro 60-0175, but an impairment in locomotor function was detected when using doses higher than 4 mg/kg in the mouse. There was a synergistic effect of low doses of Ro 60-0175 with sub-active doses of imipramine, paroxetine, citalopram and fluvoxamine; an antagonism between the highest dose of Ro 60-0175 and the active doses of paroxetine and fluoxetine was also detected. There is evidence that 5-HT(2C) receptors may be involved in the action of antidepressants which are able to boost the concentration of serotonin in the synapse, i.e. SSRIs and imipramine
ISSN:0924-977X