Alnespirone (S 20499), an agonist of 5-HT1A receptors, and imipramine have similar activity in a chronic mild stress model of depression.
A chronic mild stress (CMS) model of depression was used to study an antidepressant-like activity of alnespirone (S 20499), a selective agonist of 5-HT1A receptors. In this model, a substantial decrease in consumption of a palatable sucrose solution over time is observed in rats subjected to a variety of mild stressors. This effect can be reversed by chronic administration of various classes of antidepressant drugs. Chronic (5 weeks) treatment with alnespirone, in a dose range between 1-5 mg/kg/day, gradually and dose dependently reversed the CMS-induced reductions in sucrose consumption without any significant effects in the non-stressed control animals. The onset of action of the most active doses (2.5 and 5 mg/kg/day) and the overall efficacy of alnespirone in the CMS model were comparable to those observed following similar administration of imipramine (10 mg/kg/ day). At the lower (0.5 mg/kg/day) and higher (10 and 20 mg/kg/day) doses, alnespirone was ineffective against the CMS-induced deficit in sucrose consumption. These data provide further support for previous suggestions, based on both the clinical observations and animal data, that agonism at 5-HT1A receptors may result in antidepressant action.
Muñoz
C
C
I.R.I.S., Courbevoie, France.
Papp
M
M
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000818:Animals; D002908:Chronic Disease; D003863:Depression / Q000523:psychology*; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior / Q000187:drug effects; D005508:Food Deprivation; D007099:Imipramine / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects*; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013141:Spiro Compounds / Q000494:pharmacology*; D013315:Stress, Psychological / Q000523:psychology*; D014868:Water Deprivation
D018759:Adrenergic Uptake Inhibitors; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D013141:Spiro Compounds; C075319:alnespirone; D007099:Imipramine