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

Abstract

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.

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

“…Values represent the mean ± SEM and were analyzed by two-way ANOVA followed by Bonferroni's post hoc test: *p < 0.001 relative to Sham control, # p < 0.001 relative to OB control, N = 6-7 antidepressant-like effect, mediated by stimulation of 5-HT 6 receptors, seems to be specific, since EMD 386088 did not affect rats' activity, as measured on the OF apparatus. Our results are in line with the findings of the study by Nikiforuk et al (2011) who reported a potential antidepressant effect of EMD 386088 following its acute i.h. administration to rats.…”

“…injection of EMD 386088, blocked its reduction of immobility and increase swimming behavior. Therefore, the authors concluded that the activation of 5-HT 6 receptors might participate in the potential antidepressant activity of EMD 386088 and the hippocampus might be one of the brain structures involved in this action (Nikiforuk et al 2011).…”

“…Recently obtained results from in vitro studies have demonstrated that EMD 386088 behaves as a potent 5-HT 6 receptor partial agonist (Jastrzębska-Więsek et al 2013). Additionally, Nikiforuk et al (2011) described antidepressant properties of EMD 386088 following its intrahippocampal (i.h.) administration to rats.…”

“…Pre-clinical data indicate on the potential use of 5-HT 6 receptor antagonists as promising drugs for effective treatment of cognitive dysfunctions associated with Alzheimer's disease and schizophrenia (Fone 2008), obesity and feeding behavior (Heal et al 2008), or mood disorders (Wesołowska 2007;Wesołowska 2008;Hirano et al 2009). Also, antidepressant-like effects have been observed to be caused by 5-HT 6 receptor agonists in a number of rodent behavioral tests (Svenningsson et al 2007;Jastrzębska-Więsek et al 2010;Nikiforuk et al 2011). Two selective 5-HT 6 receptor agonists (WAY-181187 and WAY-208466) were tested for antidepressant-like activity in a modified version of the forced swim test (FST) in rats.…”

Serotonin and molecular neuroimaging in humans using PET

“…Other studies found an advantageous 5-HT 6 -mediated GABA activation and suggested antagonists in the treatment of psychiatric disorders such as schizophrenia (Marsden et al 2011;Pouzet et al 2002;Vogt et al 2000). Both, agonists and antagonists, have been implicated in the treatment of depression (Kishi et al 2010;Nikiforuk et al 2011;Wesolowska 2010) and anxiety disorders (Wesolowska 2010) as well as feeding behavior and obesity (Heal et al 2008;Holenz et al 2006). Further, 5-HT 6 receptor genes have been linked to bipolar disorder (Vogt et al 2000).…”