Graduation Semester and Year

2016

Language

English

Document Type

Thesis

Degree Name

Master of Science in Psychology

Department

Psychology

First Advisor

Qing Lin

Abstract

Ketamine is a widely used pediatric anesthetic because of its high potency in pediatric patients. Side-effects produced by ketamine anesthesia in adults are also not seen in children after ketamine use. However, several preclinical studies have shown that prolonged or repeated exposure of neonates to ketamine resulted in widespread death of neurons (neuroapoptosis) in almost all areas of the neonatal brain (Brambrink et al, 2012; Hayashi et al, 2002; Ikonomidou et al, 1999; Scallet et al, 2004; Zou et al, 2009a, b). Increasing evidence shows that this neuroapoptosis affects prenatal and neonatal brain adversely, specifically in brain areas involved in learning and memory, leading to persistent deficits in learning and cognition (Ikonomidou et al, 1999; Paule et al, 2011). Therefore, understanding the molecular mechanism underlying ketamine-induced neuroapoptosis in the neonatal brain becomes important in order to identify potential therapeutic agents that would prevent this neuroapoptosis and/or long-term cognitive deficits. In this study, we demonstrated that repeated ketamine administration (6 injections of 20 mg/kg dose given over 12 h time period) in neonatal (Post-natal Day 5-7; PND 5-7) Sprague-Dawley (SD) rats induced progressive increase in N-methyl-D-aspartate receptor (NMDAR)-mediated miniature excitatory post synaptic potentials (mEPSCs) in the anterior cingulate cortex (ACC) for up to 6 hours after the last ketamine dose. Specifically, there was a significant increase in the mEPSCs mediated by GluN2B-containing NMDARs in neurons of ACC. Taken together; these results indicated that ketamine exposure enhanced synaptic transmission mediated by GluN2B-containing NMDARs in the neonatal brain during ketamine washout period. This was significant as it showed for the first time that ketamine had subunit-specific effects on NMDARs, potentially implicating the involvement of these subunits in increased vulnerability of immature neurons of the neonatal brain to ketamine-induced neuroapoptosis.

Keywords

GluN2A, GluN2B, Excitotoxicity, Miniature EPSCs, Neonates, ACC

Disciplines

Psychology | Social and Behavioral Sciences

Comments

Degree granted by The University of Texas at Arlington

Included in

Psychology Commons

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