(+)-S-20499 - a potential antidepressant? A behavioural and neurochemical investigation in the olfactory bulbectomised rat

The study was designed to assess the potential antidepressant properties of the 5-HT1A receptor agonist, (+)-S-20499 (10 mg kg(-1) i.p.) in the olfact ory bulbectomised (OB) rat. Following 2 weeks of treatment, the rats were t ested in the elevated plus maze and the "open field". A characteristic hype ractive response was evident in the OB animals in the "open field" which wa s reversed following chronic treatment with (+)-S-20499. In the elevated pl us maze an increase in the number of open arm entries and the time spent on the open arms was observed, although this failed to reach significance. A significant decrease in beta 1 receptor affinity was evident following olfa ctory bulbectomy which was normalised by (+)-S-20499. (+)-S-20499 also sign ificantly reduced the density of 5-HT2 receptors in the sham operated (SO) animals. These studies demonstrate the usefulness of the OB rat as a screen ing test for compounds with novel putative mechanisms of action, and highli ghts the potential antidepressant properties of (+)-S-20499. (C) 1999 Elsev ier Science B.V./ECNP. All rights reserved.