Effects of repeated 5-HT6 receptor stimulation on BDNF gene expression and cell survival

•We have previously shown an acute onset by the selective 5-HT6 agonist LY-586713 on hippocampal bdnf expression.•Here we show that this effect was still present following sub-chronic (4 days), but not chronic (14 days), treatment.•The effect on 5-HT6-mediated cell survival was also dependent on a similar length of treatment.•Taken together this suggests a time dependent desensitization of a potential neurotrophic action by 5-HT6 receptors.

In support of the neurotrophic hypothesis of depression chronic antidepressant drug treatment increases brain-derived neurotrophic factor (bdnf) gene expression and neurogenesis. Regarding 5-HT active drugs, the 5-HT receptor behind these effects remains unidentified. Here we report the effect of repeated 5-HT6-receptor stimulation on bdnf expression and cell survival. The previously reported acute stimulatory action of the selective 5-HT6 agonist LY-586713 on hippocampal bdnf expression was still present following sub-chronic (4 days), but not chronic (14 days), treatment. The effect on 5-HT6-mediated cell survival was also dependent on a similar length of treatment. Hence, our study found no support for a primary effect of 5-HT6 receptors in the mediation of chronic antidepressant drug-induced up-regulation of bdnf expression or neurogenesis.