Effects of Acute and Sustained Administration of Vilazodone (EMD68843) on Monoaminergic Systems: An In Vivo Electrophysiological Study

Abstract

Vilazodone is a partial 5-HT1A receptor agonist and a selective serotonin reuptake inhibitor (SSRI). Acute administration caused a dose-dependent decrease in dorsal raphe (DR) serotonin (5-HT) neuron firing rates. Vilazodone significantly decreased DR 5-HT neuronal firing following 2-day administration, which was shown to recover completely after 14-day administration. The 2-day administration of vilazodone significantly decreased firing in ventral tegmental area dopamine neurons; this effect persisted after 14-day treatment. The firing rate of norepinephrine neurons in the locus coeruleus was not significantly altered following 2-day treatment but did decrease following 14-day treatment. In the hippocampus, 14-day treatment with vilazodone significantly enhanced tonic activation, while having no effect on 5-HT reuptake. Vilazodone produced effects similar to conventional SSRIs while also inducing alterations in monoaminergic neurons that may be associated with its 5-HT1A properties and may have a role in the field of treatment resistant depression.