G LU TA M ATE and A DDIC T ION EDITED BY B H. H , ARBARA ERMAN PhD - CO EDITED BY J F , ERRY RANKENHEIM PhD R Z. L , AYE ITTEN PhD P H. S , HILIP HERIDAN MD F F. W , ORREST EIGHT MD S R. Z , TEVEN UKIN MD HUMANA PRESS G A LUTAMATE AND DDICTION C ontemporary C linical Series Editors: Ralph Lydic and N euroscience Helen A. Baghdoyan Genetics and Genomics of Neurobehavioral Disorders, edited by Gene S. Fisch, 2003 Sedation and Analgesia for Diagnostic and Therapeutic Procedures, edited by Shobha Malviya, Norah N. Naughton, and Kevin K. Tremper, 2003 Neural Mechanisms of Anesthesia, edited by Joseph F. Antognini, Earl E. Carstens, and Douglas E. Raines, 2002 Glutamate and Addiction edited by Barbara Herman, 2002 Molecular Mechanisms of Neurodegenerative Diseases edited by Marie-Françoise Chesselet, 2000 Contemporary Clinical Neuroscience G A LUTAMATE AND DDICTION Edited by B H. H , ARBARA ERMAN PhD Clinical Medical Branch, Division of Treatment Research and Development National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH) Bethesda, MD Coeditors Jerry Frankenheim, PhD Pharmacology, Integrative & Cellular Neurobiology Research Branch (PICNRB) Division of Neuroscience & Behavioral Research (DNBR), National Institute on Drug Abuse (NIDA) National Institutes of Health (NIH), Bethesda, MD Raye Z. Litten, PhD Treatment Research Branch, Division of Clinical and Prevention Research National Institute on Drug Abuse (NIAAA), National Institutes of Health (NIH), Bethesda, MD Philip H. Sheridan, MD Division of Neuropharmacological Drug Products, Center for Drug Evaluation and Research Office of Drug Evaluation I, Food and Drug Administration, Rockville, MD Forrest F. Weight, MD Laboratory of Molecular and Cellular Neurobiology, Division of Intramural Clinical and Biological Research, National Institute on Drug Abuse (NIAAA) National Institutes of Health (NIH) Bethesda, MD Steven R. Zukin, MD Division of Treatment Research and Development, National Institute on Drug Abuse (NIDA) National Institutes of Health (NIH), Bethesda, MD HUMANA PRESS TOTOWA, NEW JERSEY © 2003 Humana Press Inc. 999 Riverview Drive, Suite 208 Totowa, New Jersey 07512 www.humanapress.com All rights reserved. No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise without written permission from the Publisher. The content and opinions expressed in this book are the sole work of the authors and editors, who have warranted due diligence in the creation and issuance of their work. 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Photocopy Authorization Policy: Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by Humana Press Inc., provided that the base fee of US $8.00 per copy, plus US $00.25 per page, is paid directly to the Copyright Clearance Center at 222 Rosewood Drive, Danvers, MA 01923. For those organizations that have been granted a photocopy license from the CCC, a separate system of payment has been arranged and is acceptable to Humana Press Inc. The fee code for users of the Transactional Reporting Service is: [0-89603-879-3/03 $10.00 + $00.25]. Printed in the United States of America. 10 9 8 7 6 5 4 3 2 1 Library of Congress Cataloging-in-Publication Data Glutamate and addiction / edited by Barbara H. Herman; coeditors, Jerry Frankenheim...[et al.]. p.;cm.–(Contemporary clinical neuroscience) Includes bibliographical references and index. ISBN 0-89603-879-3 (alk. paper) 1. Substance abuse–Pathophysiology. 2. Glutamic acid–Physiological effect. I. Herman, Barbara H. II. Frankenheim, Jerry. III. Series. [DNLM: 1. Substance-Related Disorders–physiopathology. 2. Glutamates–pharmacology. 3. Receptors, Glutamates–physiology. WM 270 G567 2002] RC564.G585 2002 616.86–dc21 2002190242 Acknowledgments This book is dedicated to our families and collaborators who contributed and sup- ported this effort to characterize the role of glutamatergic systems in addiction disorders and to develop new technologies for the treatment of these brain disorders. This book is also dedicated to Dr. Marian Fischman who died on October 23, 2001 during the final review phase of this book. Dr. Fischman’s contributions to the medications development of cocaine and opiate addiction were an outstanding influence in understanding the biology and treatment of addiction disorders. Finally, this book is dedicated to the phy- sicians Lawrence Kelley, MD, Jacqueline R. Honig, MD, Marc S. Myerson, MD, and the countless other valued medical personnel who brought one of us back from a near death experience during its creation. To Alexandra Samantha Herman, Robert H. Herman, Anita S. Herman And our families BHH, JF, RL, FW, SZ Preface AssemblingGlutamate and Addiction was a two-and-a-half year labor of love. As editors, we all had the same goal in mind and pursued this with a fierce dedication. We felt that it was now time for a volume clarifying for the first time the relationship between glutamatergic systems and addiction. The past decade has seen a steady and escalating progression of scientific advances that have implicated a pivotal role of glutamatergic systems in cocaine, opiate, and alcohol dependence––both the etiology of these disorders and their treatment. As editors, we met as a group several times a year to discuss the progress and the ever emerging direction of the book. As senior editor, I am personally indebted to the superb job of the coeditors attracting the very best scientists in this field to contribute their important papers to this book. To Philip H. Sheridan, MD of the Food and Drug Administration (FDA), for his mar- velous ability to attract internationally known scientists to contribute to the first section of the book on the basic physiology and pharmacology of glutamate. The five stellar chapters in this section include ones by Borges and Dingledine; Witkin, Kaminski and Rogawski; Choi and Snider; Sanchez and Jensen; and Kaul and Lipton. A special thank you to Michael A. Rogawski, MD,PhD, Epilepsy Research Section, NINDS, NIH for being an early and avid supporter of this effort and bringing to our attention valuable contribu- tors to this book. It is our hope that these five introductory chapters will provide a level playing field for all readers of this book to upgrade their basic understanding of glutamate before proceeding to the other research chapters focused on the relationship between glutamate and various addictive disorders. To Jerry Frankenheim, PhD of the National Institute on Drug Abuse, the National Institutes of Health (NIH) for his wonderful role, as senior editor of Section II, in illus- trating the role of glutamatergic systems in stimulant drugs of abuse including cocaine, amphetamine, and methamphetamine. Dr. Frankenheim displayed considerable care in editing this section. In addition, I am personally indebted to Dr. Frankenheim for his seamless job in serving as Acting Senior Editor of this volume for a two-month period when I was unavailable for this task. Section II is a truly remarkable part of the book in its thoroughness in covering virtually every aspect of the role of glutamate in stimulant drugs of abuse, with outstanding chapters by Pert, Post, and Weiss; Karler, Thai, and Calder; Wolf; Baker, Cornish, and Kalivas; Wang, Mao, and Lau; Pulvirenti; Vezina and Suto; Cadet; Burrows and Yamamoto; Itzhak, Martin, and Ali; Matsumoto and Pouw; Bisaga and Fischman; and Epping-Jordan. As we state in our dedication of this book, this effort also coincided with the tragic death of one of our beloved colleagues in the addic- tion field, Marian Fischman, PhD of Columbia University School of Medicine. Dr. Fis- chman was a vibrant human being, and one of the most vital forces in the research field of addiction medicine. A personal thank you to Adam Bisaga, MD who took over the task of writing and editing this chapter with Dr. Fischman in an extremely gracious and responsible fashion in the face of tragic circumstances. We are extremely grateful to the authors who contributed to the valued third section of the book on glutamate and opiate drugs of abuse including heroin. The world-renown scientists in this section included Mao; Trujillo; Popik; and Rasmussen. An overview of this important topic is provided by Jianren Mao, MD,PhD of Harvard University School vii viii Preface of Medicine. It is of interest to note that the researchers in this section were some of the first to provide evidence of a relationship between glutamate and various aspects of the addiction process. In the final section, the relationship between glutamate and alcohol abuse and alcohol- ism is explored. Our superb editors of Section IV are Forrest F. Weight, MD and Raye Litten,PhD, both of the National Institute of Alcohol Abuse and Alcoholism (NIAAA). Personally, I am particularly grateful for the continuous role provided by Dr. Litten, who managed to come to virtually every editorial meeting across building lines and to quickly get his section collated into a deliverable form to our publisher, Humana Press. I would like to thank Craig Adams and Elyse O’Grady of Humana Press for their superb editorial and publishing skills and their tireless efforts in cheering this effort on to its completion. Craig and Elyse supported this effort from the beginning and until its completion, with a compassion and expertise that I will forever admire. Finally, I would like to thank my institute, the National Institute on Drug Abuse, NIH, for being supremely generous in allowing me the time to pursue this effort for the last two and a half years. Particular thanks goes to Alan Leshner, Ph.D., former Director, NIDA, Glen R. Hanson, PhD,DDS, current and Acting Director, NIAA, Frank Vocci, PhD, Director, Division of Treatment Research and Development (DTR&D), NIDA and Ahmed Elkashef, MD, Chief, Clinical Medical Branch (CMB), DTR&D, NIDA for permitting this effort to occur. We also thank the institute directors of NIAAA, Enoch Gordis, MD (former director) and the present top official of the FDA Bernard A. Schwertz, DVM,PhD, Acting Principal Deputy Commissioner and the past commissioner of the FDA, Jane E. Henney, MD for enabling the participation of individuals from their respective institutions. I am personally touched by the numerous cards, letters and flowers that I received from family, friends, professional colleagues, and folks from Humana while in the hospital. Our interest in glutamatergic systems and drug abuse disorders stems back to at least 1991, when the first preclinical evidence was presented for a role of this system in the development of opiate tolerance and withdrawal (cf. 1, 2). Indeed, a few years earlier, research in the late 1980s suggested a role of glutamate in stimulant drug addiction (3). From there, we as a group launched several efforts to try to synthesize the knowledge base that was quickly accumulating in this exciting area. Thanks to the efforts of the National Institutes of Health (NIH) and the Food and Drug Administration (FDA), approaches to understanding the biological and behavioral basis of drug addiction and developing new modalities for the treatment of drug addiction are now attaining some level of consistency across the world. A highlight in this trend for unification in theory and practice, is illustrated by the conceptual writings of Alan I. Leshner, PhD former Director, National Institute on Drug Abuse, who has tirelessly pioneered to increase the research and scientific basis for understanding drug addiction as a disorder of the brain (e.g., 4, 5). A similar emphasis on drug abuse as a brain disorder is noted in the very basic preclinical research of Stephen E. Hyman, MD, former Director, National Institute on Mental Health (e.g., 6, 7). Similarly, in a monthly letter developed by the National Institute on Alcohol Abuse and Treatment (NIAAA), Enoch Gordis, MD, former Direc- tor, NIAAA has describe numerous scientific advances detailing the role of various biochemical systems in alcohol dependence and the role of medication treatment in alcohol dependence (cf., 8, 9). An esteemed partner in this endeavor is Jane Henney, MD, former Commissioner, FDA whose institute is responsible for making certain that the medications that are developed for this indication are both efficacious and safe. We very Preface ix much value the superb contributions of the authors in Section IV on glutamate and alcohol, who include Peoples; Crew, Rudolph, and Chandler; Becker and Redmond; Krystal, Petrakis, D’Souza, Mason, and Trevisan; Zieglgänsberger, Rammes, Spanagel, Danysz, and Parsons; Pasternak and Kolesnikov; and Potgieter. We all work together with these institutes and with the creative and brilliant scientists who undertake both the preclinical and clinical research to develop a rigorous science of drug addiction. It is our hope that this research will result in innovative treatments for drug abuse and addiction, and for understanding the basis of these disorders in the central nervous system. The job of characterizing the role of glutamatergic systems in addiction disorders is now off to a solid beginning. With the recent advance and approval of glutamatergic antago- nists for the indication of alcohol abuse and addiction in a variety of European countries, we have already started to witness some clinical payoff for the superbly innovative and thorough research of both preclinical and clinical sciences. We hope that this effort will launch a new decade starting in the year 2001, that will see yet even further advances in the glutamatergic field, both in the etiology and treatment of addiction disorders. Barbara H. Herman, PhD References 1. Herman, B.H., Vocci, F., Bridge, P. The effects of NMDA receptor antagonists and nitric oxide synthase inhibitors on opioid tolerance and withdrawal. Neuropsychopharmacology13: 269–292, 1995. 2. Herman, B.H. and O’Brien, C.P. Clinical medications development for opiate ad- diction: focus on nonopioids and opioid antagonists for the amelioration of opiate with- drawal symptoms and relapse prevention. Seminars in Neuroscience9: 158–172, 1997. 3. Karler, R., et al., Blockade of “reverse tolerance” to cocaine and amphetamine by MK-801.Life Sci 45: 599–606, 1989. 4. Leshner A.I., Koob G.F. Drugs of abuse and the brain. Proc Assoc Am Physicians 111:99–108, 1999. 5. Leshner A.I. Addiction is a brain disease, and it matters. Science278: 45–47, 1997. 6. Hyman S.E., Hyman S.E., Malenka R.C. Addiction and the brain: the neurobiology of compulsion and its persistence. Nat Rev Neurosci.2: 695–703, 2001. 7. Berke J.D., Hyman S.E. Addiction, dopamine, and the molecular mechanisms of memory.Neuron25: 515–532, 2000. 8. Gordis E. Advances in research on alcoholism and what they promise for future treatment and prevention. Med Health RI82:121, 1999. 9. Gordis E. The neurobiology of alcohol abuse and alcoholism: building knowledge, creating hope. Drug Alcohol Depend.51:9–11, 1998.