Alnespirone (S 20499), an Agonist of 5-HT 1A Receptors, and Imipramine Have Similar Activity in a Chronic Mild Stress Model of Depression

Abstract

MUÑOZ, C. AND M. PAPP. Alnespirone (S 20499), an agonist of 5-HT 1A receptors, and imipramine have similar activity in a chronic mild stress model of depression . PHARMACOL BIOCHEM BEHAV 63(4) 647–653, 1999.—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-HT 1A 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 nonstressed 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-HT 1A receptors may result in antidepressant action.