Undergraduate Honors Theses

Thesis Defended

Spring 2015

Document Type

Thesis

Type of Thesis

Departmental Honors

Department

Integrative Physiology

First Advisor

Dr. Christopher Lowry

Second Advisor

Dr. David Sherwood

Third Advisor

Dr. Jennifer Knight

Abstract

Major depressive disorder (MDD) is a prevalent psychiatric disorder. Though the exact mechanism of MDD onset is unknown, serotonin dysregulation is a common feature of the disease. Today, selective serotonin reuptake inhibitors (SSRIs) are a common treatment option for those suffering from MDD. These drugs act by selectively inhibiting the reuptake of serotonin into presynaptic serotonergic terminals, thus prolonging the actions of serotonin in the synapse. However, there exists another serotonin transporter, organic cation transporter 3 (OCT3) that is widely distributed throughout the brain and is presumably not a target of SSRIs. Consequently, efforts to inhibit the classical serotonin transporter using SSRIs may not be fully effective, as OCT3 remains active and would terminate the action of serotonin. OCT3 is a corticosterone-sensitive, low affinity, high-capacity, sodium-independent transporter for organic cations, including serotonin (5-hydroxytryptamine; 5-HT). OCT3 may play an important role in clearance of 5-HT from serotonergic synapses within the dorsal raphe nucleus (DRN), particularly when 5-HT is present in high concentrations. The DRN gives rise to the innervation of the majority of serotonergic innervation of the forebrain, and, therefore, OCT3 may play a role in myriad mechanisms. The specific aims of this project are to 1) elucidate the overall distribution of OCT3 within the rat DRN, 2) characterize the inhibition of serotonergic neuronal firing rates in the rat DRN as a result of autoinhibition of the 5-hydroxytryptamine (5-HT)1A receptor when OCT3 is blocked using corticosterone, an OCT3 antagonist, and 3) determine the location of this transporter in the synapse. Data collected from this project will provide further evidence of the importance of OCT3 in determining the degree of autoinhibition of serotonergic neuronal firing rates. OCT3 control of serotonergic signaling will have important implications for diverse physiological and behavioral affects of many neurological diseases, including MDD.

Available for download on Friday, December 01, 2017

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