Date of Award

5-2020

Document Type

Thesis

Degree Name

Master of Arts (MA)

College/School

College of Humanities and Social Sciences

Department/Program

Psychology

Thesis Sponsor/Dissertation Chair/Project Chair

Alan Pehrson

Committee Member

Adam Prus

Committee Member

Ruth Propper

Abstract

In recent years, there has been an increased interest in the role of glutamate, the brain’s major excitatory neurotransmitter, in MDD. There is ample evidence that glutamate dysfunction is present in patients with varying degrees of depression. With this mechanistic shift behind MDD has come a better understanding of the importance of cognitive dysfunction in depressed patients. The general view of MDD was that it was a mood disorder, however recent evidence suggests that cognitive functioning is also critical to relief of depressive symptomology. Attempts have been made to modulate excitatory neural networks using a class of glutamate receptors known as ionotropic glutamate receptors (iGlu receptors). However, drugs which act on iGlu receptors lead to harmful exocitoxic effects and cognitive dysfunctions. Another subtype of glutamate receptor known as metabotropic glutamate receptors (mGlu receptors) may play a more modulatory role in excitatory neurotransmission. In the present study we investigated the role of the mGlu 2/3 receptor subtypes in cognitive function in Long Evans rats using a modified version of the delayed-nonmatch-to-sample task (DNMS). We made two hypotheses, 1) that the DNMS is a working memory task, in which accuracy decreases with increasing inter-trial intervals (ITI), 2) that antagonism of mGlu 2/3 receptors using LY341495 would improve working memory performance on the DNMS task. In congruence with our first hypothesis, performance on the DNMS task is decreased with increasing ITIs. However, LY341495 administration (30 min IP) impaired DNMS accuracy at 3 mg/kg and increased response latencies at 1 and 3 mg/kg. Therefore, it appears that increasing neuronal glutamate is not sufficient to improve cognitive functions such as working memory in normal subjects. Future studies may want to investigate the effects of LY341495 using a biological model of depression like the chronic corticosterone model.

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