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Milestones in Drug Therapy Series Editors Michael J. Parnham, Director of Science & Technology, MediMlijeko d.o.o., Zagreb, Croatia Jacques Bruinvels, Bilthoven, The Netherlands Advisory Board J.C. Buckingham, Imperial College School of Medicine, London, UK R.J. Flower, The William Harvey Research Institute, London, UK A.G. Herman, Universiteit Antwerpen, Antwerp, Belgium P. Skolnick, National Institute on Drug Abuse, Bethesda, MD, USA For further volumes: http.//www.springer.com/series/4991 . Phil Skolnick Editor Glutamate-based Therapies for Psychiatric Disorders Volume Editor Phil Skolnick, Ph.D., D.Sc. (hon.) Director, Division of Pharmacotherapies & Medical Consequences of Drug Abuse National Institute on Drug Abuse 6001 Executive Boulevard Bethesda, MD 20892 USA
[email protected] Series Editors Prof. Dr. Michael J. Parnham Director of Science & Technology MediMlijeko d.o.o. Pozarinje 7 HR-10000 Zagreb Croatia Prof. Dr. Jaques Bruinvels Sweelincklaan 75 NL-3723 JC Bilthoven The Netherlands ISBN 978-3-0346-0240-2 e-ISBN 978-3-0346-0241-9 DOI 10.1007/978-3-0346-0241-9 Library of Congress Control Number: 2010935790 # Springer Basel AG 2010 This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, re-use of illustrations, recitation, broadcasting, reproduction on microfilms or in other ways, and storage in data banks. For any kind of use, permission of the copyright owner must be obtained. The use of general descriptive names, registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Product liability: The publishers cannot guarantee the accuracy of any information about dosage and application contained in this book. In every individual case the user must check such information by consulting the relevant literature. Disclaimer: This manuscript was written by Phil Skolnick in a private capacity. The views presented in his contributions neither represent the views of, nor are they sanctioned by, the National Institutes of Health. Cover illustration: NMDA receptor hypofunction model for schizophrenia (see chapter “Activation of group II metabotropic glutamate receptors (mGluR2 and mGluR3) as a novel approach for treatment of schizophrenia” by Douglas J. Sheffler and P. Jeffrey Conn) Cover design: deblik, Berlin Printed on acid-free paper Springer Basel AG is part of Springer Science þ Business Media (www.springer.com) Introduction Glutamate and Psychiatric Disorders: Evolution Over Five Decades Studies linking glutamatergic dysfunction to psychiatric disorders preceded the general acceptance of glutamate as a neurotransmitter [1]. Thus, over 50 years ago, Luby et al. [2] reported that administration of the dissociative anesthetic, phencyclidine, to symptom-free schizophrenics resulted in a recrudescence of both positive and negative symptoms. Almost a quarter century elapsed before it was demonstrated that both ketamine and phencyclidine [3] blocked transmission at the NMDA subtype of ionotropic glutamate receptor. These findings led to glutamate-based theories of schizophrenia (reviewed in [4, 5]) and ultimately, the demonstration of the antipsychotic actions of glutamate-based agents [6, 7]. Nonetheless, the use of glutamate-based strategies to treat psychiatric disorders has lagged behind the development of glutamate-based agents in neurological disorders, including stroke and traumatic brain injury [8, 9].