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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.

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