Date of Award

8-2021

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

Jennifer Pardo

Committee Member

Erin Kang

Abstract

Many psychiatric and neurological disorders such as major depressive disorder (MDD) and mild cognitive impairment (MCI) present with deficits across many cognitive domains including spatial memory and structural dysfunction of the hippocampus. The dorsal hippocampus is indicated to play a special role in spatial memory. Synaptic plasticity mechanisms are also critical in memory function in the hippocampus. Long-term potentiation (LTP) is one type of synaptic plasticity that is directly associated with memory function. Mechanisms of LTP increase α-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid (AMPA) receptors through n-methyl-d-aspartate (NMDA) receptor activation. Ketamine is an NMDA antagonist that has recently gained attention for its rapid and sustained effects on synaptic plasticity, improvements in depressive symptoms and improvements in cognitive performance. The extant literature suggests that ketamine increases AMPA receptor expression, LTP and other mechanisms in the hippocampus that govern cognitive performance. Furthermore, the literature suggests that ketamine administered 24 hours prior to cognitive tasks improves some aspects of memory. The mechanisms through which ketamine may produce changes in synaptic plasticity remains unknown. We sought to investigate ketamine’s effects on AMPA receptor expression in the dorsal hippocampus. We hypothesized that ketamine would produce dose-dependent improvements in spatial memory performance in the NOP task, and increases in AMPA receptor binding in the dorsal hippocampus. We found that ketamine had no effect on spatial memory performance or AMPA receptor binding, which does not support some of the previous findings in the literature. Further research is important in determining the mechanism underlying ketamine effects on synaptic mechanisms.

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