Antidepressant-like activity of EMD 386088, a 5-HT6 receptor partial agonist, following systemic acute and chronic administration to rats.

The study was designed to examine the potency of EMD 386088, a 5-HT6 receptor partial agonist, to exert antidepressant-like properties in animal models following acute and chronic intraperitoneal administration to rats. The modified rat forced swim test (FST) was utilized to examine a potential antidepressant effect of EMD 386088 after acute treatment (30 min before the test) and three times in a 24-h administration scheme (24 h, 5 h, and 30 min prior to the FST). The olfactory bulbectomy (OB) model was used to assess its antidepressant-like properties after chronic treatment (the drug was administered once daily for 14 days). EMD 386088 showed an antidepressant-like effect in all conducted tests. Its activity in FST after its acute administration (5 mg/kg) was blocked by the selective 5-HT6 receptor antagonist SB 271046. The obtained results seem to be specific, as there was no observed locomotor stimulation by the drug given at a lower/antidepressant dose. In the three times in the 24-h treatment scheme, EMD 386088 (2.5 mg/kg) exerted antidepressant properties in FST as well as increased locomotor activity in the open field test. Chronic administration of EMD 386088 (2.5 mg/kg) significantly improved the learning deficit in OB rats without affecting performance in Sham-operated (SH) animals in the passive avoidance test, and reduced OB-related rats' locomotor hyperactivity, but did not change the number of rearing + peeping episodes. The obtained findings suggest that EMD 386088 produces antidepressant-like activity after systemic acute and chronic administration which may result from direct stimulation of 5-HT6 receptors.