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Assessing the Effects of Ketamine on the Temporal Gene Expression of N-Methyl-D-Aspartate (NMDA) Receptors in the Brains of Rats

Paniaua-Ugarte, Claudia Assessing the Effects of Ketamine on the Temporal Gene Expression of N-Methyl-D-Aspartate (NMDA) Receptors in the Brains of Rats. 2023. Radford University, Thesis. Radford University Scholars' Repository.

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Abstract

Schizophrenia is one of the most debilitating psychiatric disorders worldwide. Symptoms of the disorder typically manifest during adolescence and are so multi-faceted that Schizophrenia is considered to be a spectrum disorder. Sex differences in symptom onset, progression, and severity have been observed, with male individuals having a higher predisposition to the disorder as well as an earlier age of onset compared to females. Currently, a definitive etiology for the disorder has not been identified. However, literature suggests that a dysregulation of glutamate signaling, with specific emphasis on N-methyl-D-aspartate receptor (NMDA) function in the brain, is linked to schizophrenia (Delisi et al., 2006; Moghaddam & Javitt, 2012; Plitman et al., 2014). Alterations in receptor function may be a result of environmental factors influencing gene expression of receptor subunits such as GRIN1 and GRIN2A during key neurodevelopment periods. To further investigate the etiology of schizophrenia and associated sex differences, the goal of the study was to assess the effects of ketamine on temporal gene expression alterations of GRIN1 and GRIN2A in the prefrontal cortex of adolescent, Long-Evans rats. Male and female rats received ketamine (30 mg/kg, i.p.) or saline injections for ten days (PND 40-49). Following administration, rats were euthanized at postnatal days 50, 55, 60, or 65 and brains were extracted to assess gene expression. The major findings were a main effect of timepoint and a 3-way interaction between treatment, sex, and timepoint for GRIN1 indicating complex alterations in gene expression following exposure. Results from this study add to a growing body of literature highlighting the intricate pathophysiology of schizophrenia and need for continued research into the etiology of the mechanism underlying the disorder. Keywords: Schizophrenia, Ketamine, NMDA Receptors, Prefrontal Cortex, GRIN1, GRIN2A, Long Evans Rats.

Item Type: Thesis
Subjects: B Philosophy. Psychology. Religion > BF Psychology
Q Science > QR Microbiology
R Medicine > RB Pathology
R Medicine > RM Therapeutics. Pharmacology
Divisions: Radford University > College of Humanities and Behavioral Sciences > Department of Psychology
Date Deposited: 09 Jul 2023 07:04
Last Modified: 09 Jul 2023 07:04
URI: http://wagner.radford.edu/id/eprint/1021

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