Graduation Term

2021

Degree Name

Master of Science (MS)

Department

Department of Psychology

Committee Chair

Byron Heidenreich

Abstract

Major Depressive Disorder (MDD) is a mental illness that affects millions of people worldwide. People diagnosed with MDD are often prescribed antidepressant drugs. Most antidepressants increase levels of serotonin (5-hydroxytryptamine, 5-HT) in the synapses between neurons. Selective-serotonin reuptake inhibitors (SSRIs), one class of antidepressants, do this by inhibiting the reuptake of serotonin released into the synapse. Serotonin neurons from the brainstem raphe nuclei affect a wide range of areas throughout the brain. Among these areas is the ventral pallidum (VP), located in the basal forebrain. Citalopram, an SSRI, has been found to increase the firing rate of action potentials of neurons in the VP of rats. The VP also projects to areas that are thought to be involved with MDD.A novel antidepressant, vortioxetine, has been developed that has multimodal actions. Vortioxetine inhibits the serotonin transporter as previous SSRI drugs do, but also is a 5-HT1A receptor agonist, 5-HT1B receptor partial agonist, and a 5-HT1D, 5-HT3, and 5-HT7 receptor antagonist. In the present study, we attempted to investigate the effects of vortioxetine on neuronal activity in the VP of urethane-anesthetized rats through extracellular single-unit electrophysiological techniques. We also measured heart rate and respiration rate, as the 5-HT system is closely related to cardiac and respiratory function. We hypothesized that vortioxetine would increase the frequency of action potentials in the VP and decrease cardiac activity and respiration rate, as citalopram did. However, the multiple actions of vortioxetine could produce qualitatively or quantitatively different effects from citalopram. It was found that increasing doses of vortioxetine slightly increased, and then dramatically decreased heart rate in the majority of rats tested. Vortioxetine most frequently increased respiration rate in the rats examined. The results of this study are compared to citalopram and assist in further understanding of the actions of vortioxetine as an effective and novel antidepressant.

KEYWORDS: Vortioxetine; Ventral Pallidum; Major Depressive Disorder, 5-HT1A agonist, electrophysiology

Access Type

Thesis-Open Access

DOI

https://doi.org/10.30707/ETD2021.20210719070603182672.37

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