MOLECULAR BIOLOGY INTELLIGENCE UNIT MOLECULAR BIOLOGY INTELLIGENCE UNIT The chapters in this book, as well as the chapters of all of the fi ve Intelligence Unit series, Robert B. Raff a and Scott M. Rawls are available at our website. R A F INTELLIGENCE UNITS FA Planaria: • Biotechnology Intelligence Unit R A Medical Intelligence Unit W L Molecular Biology Intelligence Unit S A Model for Drug Action and Abuse Neuroscience Intelligence Unit Tissue Engineering Intelligence Unit MBIU P l a n a r i a : A M o d e l f o r D r u g A c t i o n a n d A b u s e Molecular Biology Intelligence Unit Planaria: A Model for Drug Action and Abuse Robert B. Raff a, PhD Department of Pharmaceutical Sciences Temple University School of Pharmacy Philadelphia, Pennsylvania, USA Scott M. Rawls, PhD Department of Pharmaceutical Sciences Temple University School of Pharmacy Philadelphia, Pennsylvania, USA Landes Bioscience Austin, Texas USA Planaria: A Model for Drug Action and Abuse Molecular Biology Intelligence Unit Landes Bioscience Copyright ©2008 Landes Bioscience All rights reserved. No part of this book may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publisher. Printed in the USA. Please address all inquiries to the publisher: Landes Bioscience, 1002 West Avenue, Austin, Texas 78701, USA Phone: 512/ 637 6050; Fax: 512/ 637 6079 www.landesbioscience.com ISBN: 978-1-58706-332-9 While the authors, editors and publisher believe that drug selection and dosage and the specifi cations and usage of equipment and devices, as set forth in this book, are in accord with current recommend- ations and practice at the time of publication, they make no warranty, expressed or implied, with respect to material described in this book. In view of the ongoing research, equipment development, changes in governmental regulations and the rapid accumulation of information relating to the biomedical sciences, the reader is urged to carefully review and evaluate the information provided herein. Library of Congress Cataloging-in-Publication Data Planaria : a model for drug action and abuse / [edited by] Robert B. Raff a, Scott M. Rawls. p. ; cm. -- (Molecular biology intelligence unit) Includes bibliographical references and index. ISBN 978-1-58706-332-9 1. Planaria--Eff ect of drugs on. 2. Planaria as laboratory animals. 3. Pharmacology, Experimental. 4. Drug abuse--Research--Methodology. I. Raff a, Robert B. II. Rawls, Scott M. III. Series: Molecular biology intelligence unit (Unnumbered) [DNLM: 1. Planarians--drug eff ects. 2. Models, Animal. 3. Planarians--physiolo- gy. 4. Substance-Related Disorders. QX 352 P699 2008] RM301.25.P63 2008 615'.78--dc22 2008045513 Dedication To our families and our mentors, with love and gratitude About the Editors... ROBERT RAFFA is Professor of Pharmacology and Chair of the Depart- ment of Pharmaceutical Sciences at Temple University School of Pharmacy in Philadelphia, Pennsylvania. He has bachelor’s degrees in Chemical Engineering and Physiological Psychology, master’s degrees in Biomedical Engineering and Toxicology, and a doctorate in Pharmacology. He is the co-author or editor of several books on pharmacology, has published over 200 articles in refereed journals, and is active in editorial and professional society activities. His laboratory conducts NIH-funded research on drug action and abuse using the planarian model. About the Editors... SCOTT M. RAWLS is an Assistant Professor of Pharmacology in the Department of Pharmaceutical Sciences at Temple University School of Pharmacy and Research Professor at the Center for Substance Abuse Research in Philadelphia, Pennsylvania. Dr. Rawls holds a bachelor’s of science degree in Chemistry and doctorate in neuroscience. He maintains an active research laboratory funded by the National Institutes of Health (NIH) and the Pennsylvania Department of Health and has published over 40 articles in peer-reviewed journals since 1998. Dr. Rawls is active in the education of professional and graduate students. In the professional curricu- lum, Dr. Rawls coordinates the Anatomy and Physiology course and teaches the cardiovascular and renal sections in the Pharmacology course. He is the recipient of several teaching awards, including the American Association of Colleges of Pharmacy Teaching Award in 2006 and Biological Sciences Teaching Award at Washington College in 2003. Dr. Rawls is also the co-author of a pharmacology text, Netter's Illustrated Pharmacology. CONTENTS Preface ............................................................................................................xi 1. Planaria: Short Introduction .........................................................................1 Robert B. Raff a General Features ...........................................................................................................1 Reproduction .................................................................................................................2 Regeneration ..................................................................................................................3 2. Brain and Neural Networks ...........................................................................4 Kaneyasu Nishimura, Hiroshi Yamamoto, Yoshihisa Kitamura and Kiyokazu Agata Gross Structure of the Planarian CNS ....................................................................5 Domain Structure of the Planarian Brain ..............................................................5 Visualization of Neural Projections Using Fluorescent Dyes ............................7 Visualization of Neural Networks by Immunofl uorescence .............................7 3. Gene Expression in the Brain and Central Nervous System in Planarians .................................................................................................13 Katsuhiko Mineta, Kazuho Ikeo and Takashi Gojobori CNS of Planarians .....................................................................................................13 Planarian Homologs of Known Nervous System-Related Genes .................14 Planarian cDNA Microarrays and Regionalization of the CNS ....................15 4. Catecholamines in Planaria .........................................................................20 Antonio Carolei, Irene Ciancarelli and Giorgio Venturini Catecholamines ..........................................................................................................21 Acetylcholine ..............................................................................................................21 Serotonin .....................................................................................................................22 Glutamate ....................................................................................................................22 Histochemistry Studies ............................................................................................22 5. Opioids in Planaria ......................................................................................24 Antonio Carolei, Marco Colasanti and Giorgio Venturini Opioids .........................................................................................................................24 Th e Opioid System in Invertebrates ......................................................................25 Opioids in Planaria ...................................................................................................25 Opioid Receptor Subtypes in Planaria .................................................................26 Opioid Dependence in Planaria .............................................................................26 Cannabinoids and Opioids in Planaria ................................................................27 Endogenous Opioid Alkaloids in Flatworms .....................................................28 6. Nitric Oxide in Lower Invertebrates............................................................31 Marco Colasanti and Giorgio Venturini Nitric Oxide in Porifera ...........................................................................................32 Nitric Oxide in Cnidaria .........................................................................................33 Nitric Oxide in Platyhelminthes ...........................................................................35 7. Second Messenger Systems in Planaria ........................................................40 Scott M. Rawls Second Messenger Overview ..................................................................................40 Nitric Oxide ................................................................................................................41 Nitric Oxide and Planarians ...................................................................................42 cAMP and CREB .....................................................................................................45 cAMP in Planarians..................................................................................................48 8. Planaria as Model in Drug Abuse Research .................................................53 Robert B. Raff a Neurochemical Pathways.........................................................................................53 Use Schedules .............................................................................................................55 Poly-Drug Abuse ........................................................................................................55 Planarians as Model ..................................................................................................55 Establishment of the Planarian Model .................................................................56 9. Physical Dependence and Withdrawal in Planarians .................................63 Robert B. Raff a Opioids .........................................................................................................................64 Cocaine ........................................................................................................................67 Benzodiazepines ........................................................................................................68 Cannabinoid ...............................................................................................................71 Amphetamines ...........................................................................................................72 10. Drug Combinations and Isoboles ................................................................75 Ronald J. Tallarida Drug Additivity and Isobolographic Analysis ...................................................75 Experiments with Drug Combinations ...............................................................78 Drug Combinations in Planaria ............................................................................79 11. Analysis of Behavior in the Planarian Model ..............................................83 Cindy L. Nicolas, Charles I. Abramson and Michael Levin A Brief History of Learning Research in Planaria ............................................84 Learning .......................................................................................................................85 Where Are We Now? ................................................................................................87 Th e Future of Studies in Planarian Behavior ......................................................88 12. Th e Planarian Regeneration Model as a Context for the Study of Drug Eff ects and Mechanisms ...............................................................................95 Néstor J. Oviedo and Michael Levin Introduction to Planarian Regeneration .............................................................95 Regeneration as a Unique Context for the Study of Drug Eff ects and Addiction ........................................................................................................96 Evolutionary, Pharmacological and Behavioral Studies in Planarians .........99 Modern Planarian Research—Th e Molecular Age ...........................................99 Appendix ....................................................................................................105 Index ...........................................................................................................135 EDITORS Robert B. Raff a Department of Pharmaceutical Sciences Temple University School of Pharmacy Philadelphia, Pennsylvania, USA Email: robert.raff [email protected] Chapters 1, 8, 9 Scott M. Rawls Department of Pharmaceutical Sciences Temple University School of Pharmacy Philadelphia, Pennsylvania, USA Email: [email protected] Chapter 7 CONTRIBUTORS Note: Email addresses are provided for the corresponding authors of each chapter. Charles I. Abramson Marco Colasanti Department of Psychology Dipartimento di Biologia Oklahoma State University Università di Roma Tre Stillwater, Oklahoma, USA Viale Marconi Chapter 11 Roma, Italy Email: [email protected] Kiyokazu Agata Chapters 5, 6 Department of Biophysics Graduate School of Science Takashi Gojobori Kyoto University Center for Information Biology and DNA Kitashirakawa-Oiwake Databank for Japan Sakyo-ku, Kyoto, Japan National Institute of Genetics Email: [email protected] Yata, Mishima Chapter 2 Shizuoka, Japan Email: [email protected] Antonio Carolei Chapter 3 Department of Neurology University of L’Aquila Kazuho Ikeo L’Aquila, Italy Center for Information Biology and DNA Chapters 4, 5 Databank for Japan National Institute of Genetics Irene Ciancarelli Yata, Mishima Department of Neurology Shizuoka, Japan University of L’Aquila Chapter 3 L’Aquila, Italy Chapter 4