Undergraduate Honors Theses

Thesis Defended

Spring 2019

Document Type

Thesis

Type of Thesis

Departmental Honors

Department

Psychology & Neuroscience

First Advisor

Linda Watkins

Second Advisor

Heidi Day

Third Advisor

Christopher Lowry

Fourth Advisor

Andrew Kwilasz

Abstract

The demyelinating and inflammatory disorder multiple sclerosis (MS) primarily causes paralysis. However, MS also causes secondary symptoms, including: chronic pain, memory deficits, and depression. Work in our lab has shown that antagonism of toll-like 2/4 receptors with (+)-naltrexone ([+]-NTX) can reverse chronic pain and memory deficits in experimental autoimmune encephalomyelitis (EAE), a rat model of MS. We thus hypothesized that (+)-NTX would also reverse the expression of anhedonia, a symptom of depression defined as an inability to experience pleasure, as measured by saccharin preference testing within EAE. Four separate cohorts of male Dark Agouti and Sprague Dawley rats were tested. Two cohorts of each strain helped characterize saccharin drinking behavior within and outside the context of EAE. Another two cohorts from each strain were utilized to examine (+)-NTX’s effects on EAE-induced anhedonia. A low-dose model of EAE was used to remove the confound of motor paralysis. Subjects in (+)-NTX studies received (+)-NTX or saline three times per day for two weeks fourteen days following EAE induction. Reliable drinking behavior was found in both strains with and without EAE induction. EAE modestly produced motor scores and mechanical allodynia, consistent with normal expression of low-dose EAE symptoms. (+)-NTX had no effect on motor scores. (+)-NTX significantly reversed mechanical allodynia associated with EAE. However, no effect of EAE or (+)-NTX on anhedonia-like symptoms was detected. Despite negative results, continued examination of (+)-NTX is encouraged due to its ability to reverse other secondary symptoms associated with neuroinflammation within EAE.

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