The 5-HT6 receptor agonist EMD 386088 produces antidepressant and anxiolytic effects in rats after intrahippocampal administration.

Preclinical data suggest a possible role for 5-HT6 receptors in depression and anxiety. However, the results of pharmacological studies are equivocal since both blockade and stimulation of 5-HT6 receptors may evoke antidepressant- and anxiolytic-like effects. In the present study, the effects of the 5-HT6 receptor agonist EMD 386088, administered intrahippocampally (i.hp.) to rats, were assessed in behavioral tests commonly used for evaluating antidepressant- and anxiolytic-like activities. EMD 386088 (10 and 20 μg, i.hp.) exerted a significant antidepressant-like effect as revealed by decreased duration of rats' immobility in the forced swim test. This effect was blocked by systemic administration of the selective 5-HT6 receptor antagonist SB-399885. Additionally, the anxiolytic-like activity was demonstrated in the Vogel conflict and elevated plus maze tests, as EMD 386088 reduced the number of punished responding (5-20 μg, i.hp.) and increased the percentage of open arm entries (10 and 20 μg, i.hp.). The tested 5-HT6 agonist (5-20 μg, i.hp.) affected neither distance traveled in the open field test nor motor coordination assessed in the rotarod test. The results of the present study demonstrate that the 5-HT6 agonist produces antidepressant- and anxiolytic-like effects and that the hippocampus could be one of the brain regions involved in this action.