Document Type
Honors Thesis
Abstract
Ketamine, which is widely used as a pediatric anesthetic, has been reported by our and other groups to demonstrate persistent deficits in learning and memory, and alterations in N-methyl-D-aspartate receptor (NMDAR) functioning. In neonates, γ-aminobutyric acid (GABA) is excitatory upon activation of GABAA receptors rather than its mature action of neuronal inhibition. This is due to greater Na+-K+ -2Cl- co-transporter (NKCC1) and weak K+-Cl- co-transporter (KCC2) expression in the neonatal cell membrane. Thus, bumetanide – an NKCC1 inhibitor – may prevent intracellular chloride accumulation by reducing or inhibiting GABA excitation in immature neurons. Therefore, we hypothesized that bumetanide may serve as a neuroprotectant via interfering with this GABA excitatory pathway through inhibiting NKCC1 to minimize ketamine-induced neuroexcitotoxicity. Seven-day-old rats were administered ketamine subcutaneously, with intracerebroventricular delivery of bumetanide concurrently with ketamine or vehicle. Three weeks following treatment, four groups were tested for spatial learning and memory deficits using the Morris Water Maze. Prolonged latency in learning was noted in the ketamine treated animals with deficits in recall of the target platform location. However, the bumetanide co-treatment group showed a learning rate and recall similar to the control. Thus, these results suggest a new mechanism by which neonatal ketamine-induced learning and memory deficits can be alleviated through reducing hyperactive GABAergicexcitatory neonatal synaptic signaling. Keywords: γ-aminobutyric acid, Morris Water Maze, neonatal, Na +-K+ -2Cl- co-transporter
Publication Date
5-1-2016
Language
English
License
This work is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 4.0 International License.
Recommended Citation
Stevens, Ryan, "BUMETANIDE DEMONSTRATES AMELIORATION OF LEARNING AND MEMORY DEFICITS INDUCED BY KETAMINE ADMINISTRATION IN A NEONATAL RAT MODEL" (2016). 2016 Spring Honors Capstone Projects. 18.
https://mavmatrix.uta.edu/honors_spring2016/18