Electrophysiological Investigations on the Role of Selected Serotonin Receptors and the Serotonin Transporter on Serotonin Transmission in the Rat Brain

• Main Author: Lecours, Maurice
• Other Authors: Blier, Pierre
• Language: en
• Published: Université d'Ottawa / University of Ottawa 2014
• Subjects: Depression; Vortioxetine; Hippocampus; Electrophysiology; Serotonin; Lu AA21004; Multimodal Antidepressant
• Online Access: http://hdl.handle.net/10393/30400; http://dx.doi.org/10.20381/ruor-3484

This study assessed the in vivo effects of various serotonin (5-HT) receptor modulators on 5-HT neurotransmission in the rat hippocampus. Vortioxetine, humanized-vortioxetine, and escitalopram blocked the 5-HT transporter, but similar to ipsapirone did not dampen the sensitivity of postsynaptic 5-HT1A receptors. Long-term administration of all treatments increased the tonic activation of postsynaptic 5-HT1A heteroreceptors, an effect common to all antidepressants. Vortioxetine decreased the function of the terminal 5-HT1B autoreceptor under high but not a low degree of activation, thus showing that its partial agonism led to increased 5-HT release and that long-term administration results in the desensitization of terminal 5-HT1B autoreceptors. Vortioxetine overcame the effects of 5-HT1B and 5-HT3 receptor agonists. This study was unable to determine the involvement of 5-HT7 receptor antagonism exerted by vortioxetine affects 5-HT neurotransmission. Therefore, vortioxetine would appear to exert different actions, via transporter and receptor activity, on the serotonergic system in the hippocampus, consistent with its unique pharmacological profile.