Antioxidant Treatment with N-acetyl Cysteine Prevents the Development of Cognitive and Social Behavioral Deficits that Result from Perinatal Ketamine Treatment

Frontiers in Behavioral Neuroscience
Aarron PhensySven Kroener


Alterations of the normal redox state can be found in all stages of schizophrenia, suggesting a key role for oxidative stress in the etiology and maintenance of the disease. Pharmacological blockade of N-methyl-D-aspartic acid (NMDA) receptors can disrupt natural antioxidant defense systems and induce schizophrenia-like behaviors in animals and healthy human subjects. Perinatal administration of the NMDA receptor (NMDAR) antagonist ketamine produces persistent behavioral deficits in adult mice which mimic a range of positive, negative, and cognitive symptoms that characterize schizophrenia. Here we tested whether antioxidant treatment with the glutathione (GSH) precursor N-acetyl-cysteine (NAC) can prevent the development of these behavioral deficits. On postnatal days (PND) 7, 9 and 11, we treated mice with subanesthetic doses (30 mg/kg) of ketamine or saline. Two groups (either ketamine or saline treated) also received NAC throughout development. In adult animals (PND 70-120) we then assessed behavioral alterations in a battery of cognitive and psychomotor tasks. Ketamine-treated animals showed deficits in a task of cognitive flexibility, abnormal patterns of spontaneous alternation, deficits in novel-object recognition, as w...Continue Reading


Oct 1, 1991·The American Journal of Psychiatry·Daniel C Javitt, S R Zukin
Feb 1, 1990·Archives of General Psychiatry·D L Braff, Mark A Geyer
Jul 1, 1986·Pharmacology, Biochemistry, and Behavior·N R SwerdlowG F Koob
Sep 1, 1974·European Journal of Pharmacology·E H Ellinwood, R L Balster
Mar 1, 1994·The American Journal of Psychiatry·W Perry, D L Braff
Mar 1, 1996·The American Journal of Psychiatry·Michael F Green
Aug 20, 1996·Proceedings of the National Academy of Sciences of the United States of America·M LaruelleR B Innis
Jan 1, 1996·The Journal of Neuropsychiatry and Clinical Neurosciences·L P KarperJohn H Krystal
Feb 28, 1997·Schizophrenia Research·Jean Addington, Donald Addington
Mar 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·A BreierD Pickar
Mar 1, 1996·Schizophrenia Research·S P Mahadik, S Mukherjee
Sep 1, 1997·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·A K MalhotraA Breier
Sep 10, 1999·Acta Psychiatrica Scandinavica·H HäfnerW an der Heiden
Oct 13, 2000·The European Journal of Neuroscience·K Q DoM Cuénod
Oct 25, 2000·Synapse·W Almaguer-MelianJ A Bergado
Aug 15, 2001·Scandinavian Journal of Psychology·A P Weiss, S Heckers
Feb 12, 2002·Neuroscience and Biobehavioral Reviews·Robert Lalonde
Jul 2, 2002·Archives of General Psychiatry·John H KrystalBita Moghaddam
Dec 20, 2002·The Journal of Pharmacology and Experimental Therapeutics·Cheng WangKenneth M Johnson
Aug 19, 2003·Journal of the American Academy of Child and Adolescent Psychiatry·Jon McClellanStefanie A Hlastala
Aug 23, 2003·Behavioral Neuroscience·Mark Renato StefaniBita Moghaddam
Oct 12, 2004·Behavioural Brain Research·Maria Noêmia M de LimaNadja Schröder
Nov 9, 2004·Schizophrenia Research·Keith H NuechterleinRobert K Heaton
Nov 9, 2004·Schizophrenia Research·Michael F GreenRobert K Heaton
Jan 5, 2005·The British Journal of Psychiatry : the Journal of Mental Science·Eve C JohnstoneStephen M Lawrie
Jul 14, 2005·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Stan B FlorescoMaric T L Tse
Jan 18, 2006·Disease Markers·Jeffrey K YaoRavinder Reddy
Feb 24, 2006·Comprehensive Psychiatry·Vasilis P BozikasAthanasios Karavatos
Feb 24, 2006·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Kenji HashimotoMasaomi Iyo
Oct 4, 2006·Brain Research Reviews·Teresa Marie du Bois, Xu-Feng Huang
Mar 16, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Gareth R I BarkerE Clea Warburton
Oct 9, 2007·Proceedings of the National Academy of Sciences of the United States of America·René GysinKim Q Do
Nov 16, 2007·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Suzie LavoieKim Q Do
Nov 21, 2007·Schizophrenia Research·Jean AddingtonDiana Perkins
Jan 9, 2008·Archives of General Psychiatry·Tyrone D CannonRobert Heinssen
Mar 11, 2008·Brain and Cognition·Paul ElingRoald Maes
Mar 28, 2008·Behavioural Brain Research·Brian Villumsen BrobergChristina Kurre Olsen
Dec 27, 2008·Behavioural Brain Research·Stan B FlorescoTakeshi Enomoto
Mar 28, 2009·Schizophrenia Bulletin·Oliver D Howes, Shitij Kapur
May 5, 2009·Pharmacology, Biochemistry, and Behavior·Leon G ColemanFulton T Crews
Jun 2, 2009·Current Opinion in Neurobiology·Kim Q DoMichel Cuenod
Jun 30, 2009·Biological Psychiatry·Stefania SchiavoneKarl-Heinz Krause
Jul 1, 2009·Experimental Brain Research·Amanda LyallChristopher Paul Turner
Sep 5, 2009·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Agnieszka NikiforukPiotr Popik
Nov 17, 2009·Current Pharmaceutical Design·Richard B Mailman, Vishakantha Murthy
Feb 19, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Pascal SteulletKim Q Do
May 4, 2010·Brain Research Bulletin·Laura C AmannSteven J Siegel
May 26, 2010·Cognitive, Affective & Behavioral Neuroscience·Jared W YoungVictoria B Risbrough
Jul 17, 2010·The International Journal of Neuropsychopharmacology·Jeremy W GawrylukL Trevor Young
Jul 24, 2010·Antioxidants & Redox Signaling·Cynthia A Massaad, Eric Klann
Aug 18, 2010·Antioxidants & Redox Signaling·Daisuke Matsuzawa, Kenji Hashimoto
Aug 27, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Silvia SorceKarl-Heinz Krause
Sep 28, 2010·European Journal of Pharmacology·Kwok Ho Christopher ChoyMaarten van den Buuse
Oct 27, 2010·Neuroscience and Biobehavioral Reviews·Byron K Y Bitanihirwe, Tsung-Ung W Woo
Feb 12, 2011·Current Topics in Behavioral Neurosciences·Susan B Powell
Apr 30, 2011·Neurobiology of Learning and Memory·William S Stone, Xiaolu Hsi
Sep 3, 2011·Current Neuropharmacology·C VenâncioT Summavielle
Dec 14, 2011·Trends in Neurosciences·David A LewisDavid W Volk
Mar 1, 2012·Current Topics in Behavioral Neurosciences·Susan B PowellMark A Geyer
May 5, 2012·Schizophrenia Research·Xiang Yang ZhangThomas R Kosten
Oct 3, 2012·Handbook of Experimental Pharmacology·Richard S E Keefe, Philip D Harvey
Oct 3, 2012·Handbook of Experimental Pharmacology·Jared W YoungMark A Geyer
Feb 2, 2013·Trends in Pharmacological Sciences·M BerkO M Dean
May 21, 2013·Biological Psychiatry·Joshua FlatowBrian J Miller
Aug 9, 2013·JAMA Psychiatry·René S Kahn, Richard S E Keefe
Dec 19, 2013·Current Pharmaceutical Design·Lakshmi RajagopalHerbert Y Meltzer
Dec 3, 2014·Neuroscience and Biobehavioral Reviews·Ashwini RajasekaranMonojit Debnath
Jun 28, 2015·Behavioural Brain Research·Juan Facundo MoriciNoelia V Weisstaub
Jan 9, 2016·Neuroscience and Biobehavioral Reviews·Rachel Anne Hill
Jan 15, 2016·Nature Reviews. Neuroscience·Giles E Hardingham, Kim Q Do
Nov 30, 2016·Psychological Medicine·M Rapado-CastroO M Dean

Related Concepts

Laboratory mice
Stereotyped Behavior
N-Methyl-D-Aspartate Receptors

Trending Feeds


Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Synthetic Genetic Array Analysis

Synthetic genetic arrays allow the systematic examination of genetic interactions. Here is the latest research focusing on synthetic genetic arrays and their analyses.

Congenital Hyperinsulinism

Congenital hyperinsulinism is caused by genetic mutations resulting in excess insulin secretion from beta cells of the pancreas. Here is the latest research.

Neural Activity: Imaging

Imaging of neural activity in vivo has developed rapidly recently with the advancement of fluorescence microscopy, including new applications using miniaturized microscopes (miniscopes). This feed follows the progress in this growing field.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Epigenetic Memory

Epigenetic memory refers to the heritable genetic changes that are not explained by the DNA sequence. Find the latest research on epigenetic memory here.

Cell Atlas of the Human Eye

Constructing a cell atlas of the human eye will require transcriptomic and histologic analysis over the lifespan. This understanding will aid in the study of development and disease. Find the latest research pertaining to the Cell Atlas of the Human Eye here.

Femoral Neoplasms

Femoral Neoplasms are bone tumors that arise in the femur. Discover the latest research on femoral neoplasms here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.