Partial role of 5-HT2 and 5-HT3 receptors in the activity of antidepressants in the mouse forced swimming test.
The present study was designed to evaluate the roles of 5-HT2 and 5-HT3 receptors in the mouse forced swimming test, by using selective agonists and antagonists of 5-HT(2A/C) and 5-HT3 receptor sites. Agonists/antagonists and antidepressants were administered 45 min and 30 min, respectively, prior to testing. Pretreatment with (+/-)-2,5-dimethoxy-4-iodoamphetamine (DOI) (4 mg/kg, i.p.) or 2-methyl-5-HT (4 mg/kg, i.p.) had no effect on the anti-immobility effects of any antidepressant tested. Prior administration of ritanserin (4 mg/kg, i.p.) or ketanserin (8 mg/kg, i.p.), on the other hand, potentiated the effects of sub-active doses of imipramine (8 mg/kg, i.p.) and desipramine (16 mg/kg, i.p.) but not of maprotiline (8 mg/kg, i.p.), fluoxetine (16 mg/kg, i.p.), citalopram (16 mg/kg, i.p.) or fluvoxamine (8 mg/kg, i.p.). Pretreatment with ondansetron (1 X 10(-5) mg/kg, i.p.) enhanced the antidepressant-like effects of sub-active doses of the selective serotonin reuptake inhibitors. The results of the present study suggested that, in the forced swimming test, the selective serotonin reuptake inhibitors act partially through 5-HT3 receptor sites, whereas the tricyclic antidepressants exert effects at 5-HT(2A/C) receptor sites. Anti-immobility effects of the selective noradrenaline reuptake inhibitor, maprotiline, do not seem to be mediated by 5-HT(2A/C) or 5-HT3 receptor function.
Redrobe
J P
JP
GIS Médicament, JE 2027 Neurobiologie de l'anxieté, Faculty of Medicine, Nantes, France.
Bourin
M
M
D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology*; D015283:Citalopram / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D004347:Drug Interactions; D005473:Fluoxetine / Q000494:pharmacology; D016666:Fluvoxamine / Q000494:pharmacology; D007099:Imipramine / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008376:Maprotiline / Q000494:pharmacology; D051379:Mice; D017294:Ondansetron / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology*; D044406:Receptors, Serotonin, 5-HT3; D016713:Ritanserin / Q000494:pharmacology; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013550:Swimming
D000662:Amphetamines; D000928:Antidepressive Agents; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D005473:Fluoxetine; D015283:Citalopram; D016713:Ritanserin; D008376:Maprotiline; D012701:Serotonin; D017294:Ondansetron; C045918:2-methyl-5-HT; D007650:Ketanserin; D016666:Fluvoxamine; D007099:Imipramine; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; D003891:Desipramine