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

• Published in: European neuropsychopharmacology Vol. 9; no. 1; pp. 21 - 27
• Main Authors: McGrath, C, Norman, T.R
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 1999
• Subjects: (+)-S-20499; 5-HT 2 receptor binding; 8-Hydroxy-2-(di-n-propylamino)tetralin - pharmacology; Adrenergic beta-Antagonists - metabolism; Animals; Antidepressive Agents - pharmacology; Anxiety - metabolism; Anxiety - psychology; Behavior, Animal - drug effects; Body Temperature - drug effects; Brain Chemistry - drug effects; Male; Nerve Tissue Proteins - metabolism; Olfactory Bulb - physiology; Olfactory bulbectomy; Propanolamines - metabolism; Rats; Rats, Sprague-Dawley; Receptor, Serotonin, 5-HT2A; Receptors, Adrenergic, beta-1 - drug effects; Receptors, Adrenergic, beta-1 - metabolism; Receptors, Serotonin - drug effects; Serotonin Receptor Agonists - pharmacology; Spiro Compounds - pharmacology; β1 receptor; Olfactory bulbectomy; β1 receptor; (+)-S-20499; 5-HT 2 receptor binding
• ISSN: 0924-977X; 1873-7862
• DOI: 10.1016/S0924-977X(97)00103-X

The study was designed to assess the potential antidepressant properties of the 5-HT 1A receptor agonist, (+)-S-20499 (10 mg kg −1 i.p.) in the olfactory bulbectomised (OB) rat. Following 2 weeks of treatment, the rats were tested in the elevated plus maze and the “open field”. A characteristic hyperactive response was evident in the OB animals in the “open field” which was reversed following chronic treatment with (+)-S-20499. In the elevated plus 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 β1 receptor affinity was evident following olfactory bulbectomy which was normalised by (+)-S-20499. (+)-S-20499 also significantly reduced the density of 5-HT 2 receptors in the sham operated (SO) animals. These studies demonstrate the usefulness of the OB rat as a screening test for compounds with novel putative mechanisms of action, and highlights the potential antidepressant properties of (+)-S-20499.