title: Neonatal ketamine exposure causes impairment of long-term synaptic plasticity in the anterior cingulate cortex of rats.
abstract: Ketamine, a dissociative anesthetic most commonly used in many pediatric procedures, has been reported in many animal studies to cause widespread neuroapoptosis in the neonatal brain after exposure in high doses and/or for a prolonged period. This neurodegenerative change occurs most severely in the forebrain including the anterior cingulate cortex (ACC) that is an important brain structure for mediating a variety of cognitive functions. However, it is still unknown whether such apoptotic neurodegeneration early in life would subsequently impair the synaptic plasticity of the ACC later in life. In this study, we performed whole-cell patch-clamp recordings from the ACC brain slices of young adult rats to examine any alterations in long-term synaptic plasticity caused by neonatal ketamine exposure. Ketamine was administered at postnatal day 4-7 (subcutaneous injections, 20mg/kg given six times, once every 2h). At 3-4weeks of age, long-term potentiation (LTP) was induced and recorded by monitoring excitatory postsynaptic currents from ACC slices. We found that the induction of LTP in the ACC was significantly reduced when compared to the control group. The LTP impairment was accompanied by an increase in the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-mediated excitatory synaptic transmission and a decrease in GABA inhibitory synaptic transmission in neurons of the ACC. Thus, our present findings show that neonatal ketamine exposure causes a significant LTP impairment in the ACC. We suggest that the imbalanced synaptic transmission is likely to contribute to ketamine-induced LTP impairment in the ACC.
authors.affiliation: Institute for Biomedical Sciences of Pain, Capital Medical University, Beijing, China; Department of Psychology, College of Science, The University of Texas at Arlington, Arlington, TX, USA; Institute for Biomedical Sciences of Pain and Institute for Functional Brain Disorders, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: R-R
authors.initials: RR
authors.lastname: Wang
authors.affiliation: Department of Psychology, College of Science, The University of Texas at Arlington, Arlington, TX, USA.
authors.forename: J-H
authors.initials: JH
authors.lastname: Jin
authors.affiliation: Department of Psychology, College of Science, The University of Texas at Arlington, Arlington, TX, USA.
authors.forename: A W
authors.initials: AW
authors.lastname: Womack
authors.affiliation: Department of Psychology, College of Science, The University of Texas at Arlington, Arlington, TX, USA.
authors.forename: D
authors.initials: D
authors.lastname: Lyu
authors.affiliation: Department of Psychology, College of Science, The University of Texas at Arlington, Arlington, TX, USA.
authors.forename: S S
authors.initials: SS
authors.lastname: Kokane
authors.affiliation: Department of Psychology, College of Science, The University of Texas at Arlington, Arlington, TX, USA.
authors.forename: N
authors.initials: N
authors.lastname: Tang
authors.affiliation: Department of Psychology, College of Science, The University of Texas at Arlington, Arlington, TX, USA.
authors.forename: X
authors.initials: X
authors.lastname: Zou
authors.affiliation: Department of Psychology, College of Science, The University of Texas at Arlington, Arlington, TX, USA. Electronic address: qilin@uta.edu.
authors.forename: Q
authors.initials: Q
authors.lastname: Lin
authors.affiliation: Institute for Biomedical Sciences of Pain, Capital Medical University, Beijing, China; Institute for Biomedical Sciences of Pain and Institute for Functional Brain Disorders, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China. Electronic address: chenjun@ccmu.edu.cn.
authors.forename: J
authors.initials: J
authors.lastname: Chen
mesh_terms: D000778:Anesthetics, Dissociative / Q000633:toxicity*; D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D006179:Gyrus Cinguli / Q000187:drug effects* / Q000254:growth & development* / Q000503:physiopathology; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D007649:Ketamine / Q000633:toxicity*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects / Q000254:growth & development / Q000502:physiology; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D046509:Tissue Culture Techniques
chemical_list: D000778:Anesthetics, Dissociative; D018091:Receptors, AMPA; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine
keywords: anterior cingulate cortex; excitatory synaptic transmission; inhibitory synaptic transmission; ketamine; long-term potentiation