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
License
This work is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 4.0 International License.
Recommended Citation
Kokane, Saurabh, "The effects of ketamine exposure on NMDA receptor mediated synaptic transmission in the developing brain - A mechanistic study of ketamine-induced neuroapoptosis" (2016). Psychology Theses. 146.
https://mavmatrix.uta.edu/psychology_theses/146
Comments
Degree granted by The University of Texas at Arlington