Assessment of CNS toxicity caused by pediatric exposure to ketamine and other general anesthetics. This study is a collaborative effort with CDER.Ketamine is primarily used for the induction and maintenance of general anesthesia, usually in combination with some sedative drugs. Ketamine is used in both human and veterinary medicine. These studies are working with three organisms having similar genomes to humans (zebra fish, rats, and monkeys) to provide information on ways to minimize risk associated with the pediatric use of general anesthetics.Previous ketamine studies with monkeys have helped to identify developmental periods during which sensitivity to ketamine is greatest. The offspring of these animals will be used for further research on the effects of pediatric exposure to general anesthetics and will result in the development of translatable biomarkers for studying pediatric products.These studies will provide information on ways to minimize risk associated with the pediatric use of general anesthetics.For more information on this research, watch the <a href= http://www.youtube.com/user/USFoodandDrugAdmin#p/u/16/t_ajURa-W7Q target=”_blank”>SmartTots video</a>.This project was terminated due to an unacceptably high risk to laboratory animals.maina. Complete research on additional measures of cognitive function in laboratory animals exposed to ketamine10/31/2010Completed10/31/2010mainb. Complete assessment of research findings1/1/2011Completed1/18/2011mainc. Develop draft technical report/manuscript/publication on cognitive function in laboratory animal offspring exposed to ketamine2/1/2011Completed2/10/2011maind. Complete the peer review (NCTR and other FDA researchers) of draft technical report, manuscript, and/or publication4/1/2011Completed4/1/2011maine. Obtain NCTR Center Director approval on the draft technical report, manuscript, and/or publication via the document tracking system5/1/2011Completed5/1/2011mainf. Submit final technical report, manuscript, and/or publication describing the cognitive assessments of laboratory animal offspring exposed to ketamine to a scientific journal6/1/2011Completed6/1/2011<b>Accomplishment: </b>NCTR investigators have demonstrated that a single 24-hour exposure to ketamine anesthesia during a sensitive period of brain development results in long-lasting deficits in brain function in nonhuman primates and provides proof-of-concept that general anesthesia administered to pediatric patients during critical periods of brain development could result in subsequent functional deficits. Nonhuman primates were exposed to ketamine for 24 hours on day 5 or 6 after birth and were tested for aspects of learning, motivation, color discrimination, and short-term memory using the NCTR Operant Test Battery (OTB) beginning at 7 months of age. At 10 months of age, the ketamine-exposed animals were significantly outperformed by the control animals. These treated animals, exposed to a single 24-hour exposure to anesthesia, continue to manifest cognitive impairments at over 3.5 years of age. These studies were supported by the National Institute of Child Health and Human Development (NICHD), the Center for Drug Evaluation and Research (CDER), and NCTR. A manuscript describing the results of this study has recently been accepted for publication in the journal Neurotoxicology and Teratology.maina. Furnish specialized animal laboratory10/31/2009Completed12/31/2009mainb. Approve all three protocols1/31/2010Completed2/18/2010mainc. Begin assessing ketamine’s effect on laboratory animal embryos2/28/2010Completed2/19/2010maind. Assess ketamine's effect on cranial and spinal motor neurons4/30/2010Completed4/25/2010maine. Effect of ketamine on neuronal signaling enzyme activity in laboratory animal6/30/2010Completed6/16/2010mainf. Determine neuronal levels of ketamine treated laboratory animals8/31/2010Completed8/30/2010maing. Determine if ketamine affects neuronal gene expressions8/31/2010<i>(1/30/2011)</i>Completed12/31/2010mainh. Complete research on effects of ketamine on laboratory animals11/1/2010Completed11/1/2010maini. Completed assessment of research findings11/15/2010Completed11/15/2010mainj. Develop draft technical report/manuscript/publication on ketamine's effect on laboratory animals11/30/2010Completed11/30/2011maink. Complete the peer review (NCTR and other FDA researchers) of draft technical report, manuscript, and/or publication2/1/2011Completed2/1/2011mainl. Obtain NCTR Center Director approval on the draft technical report, manuscript, and/or publication via the document tracking system3/1/2011Completed3/1/2011mainm. Submit final technical report, manuscript, and/or publication on ketamine's effect on laboratory animal to a scientific journal4/1/2011Completed4/1/2011CNSCentral Nervous Systemketaminedrug causing analgesic, anesthetic, elevated blood pressure and other effects in humanscranial and spinal motor neuronscells carrying electric signals coding for cognition sensation movement and other functionsneuronalnerve cell that transmits impulsesenzymeprotein controlling biochemical reactionsneuronal gene expressionsthe process by which a gene's coded information is converted into the structures operating in a cellhttp://www.fda.gov/AboutFDA/Transparency/track/ucm203296.htmFDA-TRACK NCTR Dashboardhttp://www.fda.gov/AboutFDA/Transparency/track/ucm252974.htmFDA-TRACK Research Glossary਍††਍਍਍਍਍਍਍