Anxiolytic-like effects observed in rats exposed to the elevated zero-maze following treatment with 5-HT2/5-HT3/5-HT4 ligands

• Published in: Scientific reports 2014-01, Vol.4 (1), p.3881-3881, Article 3881
• Main Authors: Bell, Rob, Duke, Aaron A., Gilmore, Paula E., Page, Deaglan, Bègue, Laurent
• Format: Article
• Language: English
• Subjects: 631/378; 631/477; 631/601/18; 64/86; Aniline Compounds - therapeutic use; Animals; Anti-Anxiety Agents - therapeutic use; Anxiety; Anxiety - drug therapy; Anxiolytics; Behavior, Animal - drug effects; Bridged Bicyclo Compounds, Heterocyclic - therapeutic use; Diazepam; Diazepam - therapeutic use; Experiments; Humanities and Social Sciences; Male; Maze Learning - drug effects; multidisciplinary; Oxazines - therapeutic use; Piperidines - therapeutic use; Propane - analogs & derivatives; Propane - therapeutic use; Pyrazines - therapeutic use; Rats; Rats, Sprague-Dawley; Receptors, Serotonin - physiology; Science; Serotonin - metabolism; Serotonin Antagonists - therapeutic use; Serotonin Receptor Agonists - therapeutic use; Serotonin S2 receptors; Serotonin S3 receptors; Serotonin S4 receptors; Spiro Compounds - therapeutic use; Sulfonamides - therapeutic use
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep03881

The present study examined the effects of administering selective 5-HT antagonists and agonists to rats tested in the elevated zero-maze (EZM) model of anxiety. The EZM paradigm has advantages over the elevated plus-maze (EPM) paradigm with respect to measuring anxiety, yet has been utilized less frequently. Three experiments were conducted each with a diazepam control (0.25, 0.5 and 0.75 mg/kg). In the first experiment, we administered the 5-HT 2C antagonist RS 102221 (0.5, 1.0 and 2.0 mg/kg) and 5-HT 2C agonist MK-212 (0.25, 0.5 and 0.75 mg/kg); in the second experiment, we administered the 5-HT 3 antagonist Y-25130 (0.1, 1.0 and 3.0 mg/kg) and 5-HT 3 agonist SR 57227A (0.1, 1.0 and 3.0 mg/kg) and in the third experiment, we administered the 5-HT 4 antagonist RS 39604 (0.01, 0.1, 1.0 mg/kg) and 5-HT 4 agonist RS 67333 (0.01, 0.1 and 0.5 mg/kg). The administration of 5-HT 2/3/4 subtype antagonists all generated behavioral profiles indicative of anxiolytic-like effects in the EZM, which was apparent from examination of both traditional and ethological measures. While little effect was observed from 5-HT 2 and 5-HT 3 agonists, the 5-HT 4 agonist RS 67333 was found to produce a paradoxical anxiolytic-like effect similar to that produced by the 5-HT 4 antagonist RS 39604. We conclude by discussing the implications of these findings.