Pharmacological evaluation of the anxiolytic-like effects of EMD 386088, a partial 5-HT6 receptor agonist, in the rat elevated plus-maze and Vogel conflict tests.

Magdalena Jastrzębska-Więsek, Agata Siwek, Anna Partyka, Monika Kubacka, Szczepan Mogilski, Anna Wasik, Marcin Kołaczkowski, Anna Wesołowska

Index: Neuropharmacology 85 , 253-62, (2014)

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Abstract

The 5-HT6 is one of the most recent additions to the 5-HT receptor family. Its pharmacological profile and anatomical distribution is suggestive of a putative role in mood disorders. Most of preclinical evidence suggests an anxiolytic-like action of 5-HT6 receptor antagonists. Evaluation the anxiolytic-like effects of EMD 386088, a partial 5-HT6receptor agonist, and its putative mechanism of action in rats. EMD 386088, administered intraperitoneally at a dose of 2.5 mg/kg evoked specific anxiolytic-like activity in the automated version of the conflict drinking Vogel and the elevated plus-maze tests visible by increasing all parameters indicating a potential anti-anxiety effect. Its activity was blocked by the selective 5-HT6 receptor antagonist SB 271046, but not by the selective GABAA/benzodiazepine receptor antagonist flumazenil. EMD 386088 did not intensify an anxiolytic-like effect produced by diazepam in the elevated plus-maze test. These findings suggest that EMD 386088, a 5-HT6 receptor agonist, produces anxiolytic-like activity after systemic administration which may result from direct stimulation of 5-HT6 receptors. Copyright © 2014 Elsevier Ltd. All rights reserved.