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Methods of BEHAVIOR ANALYSIS in NEUROSCIENCE © 2001 by CRC Press LLC METHODS & NEW FRONTIERS IN NEUROSCIENCE SERIES Series Editors Sidney A. Simon, Ph.D. Miguel A.L. Nicolelis, M.D., Ph.D. Published Titles Apoptosis in Neurobiology Yusef A. Hannun, Ph.D. and Rose-Mary Boustany, Ph.D. Methods for Neural Ensemble Recordings Miguel A.L. Nicolelis, M.D., Ph.D. © 2001 by CRC Press LLC Boca Raton London New York Washington, D.C. CRC Press Edited by Jerry J. Buccafusco Methods of BEHAVIOR ANALYSIS in NEUROSCIENCE © 2001 by CRC Press LLC Publisher/Acquiring Editor: Barbara Norwitz This book contains information obtained from authentic and highly regarded sources. Reprinted material is quoted with permission, and sources are indicated. A wide variety of references are listed. Reasonable efforts have been made to publish reliable data and information, but the author and the publisher cannot assume responsibility for the validity of all materials or for the consequences of their use. Neither this book nor any part may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, microfilming, and recording, or by any information storage or retrieval system, without prior permission in writing from the publisher. All rights reserved. Authorization to photocopy items for internal or personal use, or the personal or internal use of specific clients, may be granted by CRC Press LLC, provided that $.50 per page photocopied is paid directly to Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923 USA. The fee code for users of the Transactional Reporting Service is ISBN 0-8493-0704- X/00/$0.00+$.50. The fee is subject to change without notice. For organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged. The consent of CRC Press LLC does not extend to copying for general distribution, for promotion, for creating new works, or for resale. Specific permission must be obtained in writing from CRC Press LLC for such copying. Direct all inquiries to CRC Press LLC, 2000 N.W. Corporate Blvd., Boca Raton, Florida 33431. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation, without intent to infringe. © 2001 by CRC Press LLC No claim to original U.S. Government works International Standard Book Number 0-8493-0704-X Library of Congress Card Number 00-039762 Printed in the United States of America 1 2 3 4 5 6 7 8 9 0 Printed on acid-free paper Library of Congress Cataloging-in-Publication Data Methods of behavior analysis in neuroscience / edited by Jerry J. Buccafusco. p. cm. — (Methods and new frontiers of neuroscience) Includes bibliographical references and index. ISBN 0-8493-0704-X (alk. paper) 1. Neurosciences—Handbooks, manuals, etc. 2. Animal behavior—Handbooks, manuals, etc. 3. Laboratory animals—Psychology—Handbooks, manuals, etc. 4. Behavioral assessment—Handbooks, manuals, etc. I. Buccafusco, Jerry J. II. Series. [DNLM: 1. Behavior, Animal. 2. Neurosciences—methods. 3. Animals, Laboratory—psychology. WL 100 M5925 2000] RC343.M45 2000 616.8 ′ 027—dc21 00-039762 0704/fm/frame Page iv Tuesday, July 18, 2000 11:10 AM © 2001 by CRC Press LLC Series Preface Our goal in creating the Methods & New Frontiers in Neuroscience Series is to present the insights of experts on emerging experimental techniques and theoretical concepts that are, or will be at the vanguard of Neuroscience. Books in the series will cover topics ranging from methods to investigate apoptosis, to modern tech- niques for neural ensemble recordings in behaving animals. The series will also cover new and exciting multidisciplinary areas of brain research, such as computa- tional neuroscience and neuroengineering, and will describe breakthroughs in clas- sical fields like behavioral neuroscience. We want these to be the books every neuroscientist will use in order to get acquainted with new methodologies in brain research. These books can be given to graduate students and postdoctoral fellows when they are looking for guidance to start a new line of research. The series will consist of case-bound books of approximately 250 pages. Each book will be edited by an expert and will consist of chapters written by the leaders in a particular field. Books will be richly illustrated and contain comprehensive bibliographies. Each chapter will provide substantial background material relevant to the particular subject. Hence, these are not going to be only “ methods books.” They will contain detailed “tricks of the trade” and information as to where these methods can be safely applied. In addition, they will include information about where to buy equipment, web sites that will be helpful in solving both practical and theoretical problems, and special boxes in each chapter that will highlight topics that need to be emphasized along with relevant references. We are working with these goals in mind and hope that as the volumes become available the effort put in by us, the publisher, the book editors, and individual authors will contribute to the further development of brain research. The extent that we achieve this goal will be determined by the utility of these books. 0704/fm/frame Page v Tuesday, July 18, 2000 11:10 AM © 2001 by CRC Press LLC 0704/fm/frame Page vi Tuesday, July 18, 2000 11:10 AM © 2001 by CRC Press LLC Preface Behavioral techniques used in animals to model human diseases and to predict the clinical actions of novel drugs are as varied as the numbers of scientists who use them. For behaviors as simple as locomotor performance in an open field, there are dozens of experimental approaches and various components of movement that con- tribute to overall motor activity. As behavioral models become more complex, there is often a bewildering array of perturbations for a given task extant in the literature. Yet behavioral analysis, as a tool for the basic neuroscientist, is becoming indis- pensable as information gained at the molecular and cellular level is put into practice in fully behaving animal subjects. Since the neuroscientist trained in methodologies directed toward the molecular and cellular level does not often have experience in the intricacies of animal behav- ioral analyses, there is often much time devoted to assessing a complex literature, or to developing an approach de novo . Specialists who are recognized experts in several fields of cognitive and behavioral neuroscience have provided chapters that focus on a particular behavioral model. Each author has analyzed the literature to describe the most frequently used and accepted version of the model. Each chapter includes: (1) a well-referenced introduction that covers the theory behind, and the utility of the model; (2) a detailed and step-wise methodology; and (3) approach to data interpretation. Many chapters also provide examples of actual experiments that use the method. The primary objective of the book is to provide a reference manual for use by practicing scientists having various levels of experience who wish to use the most well-studied behavioral approaches in animal subjects to better understand the effects of disease, and to predict the effects of new therapeutic treatments on the human cognition. In view of the large numbers of transgenic animals produced on an almost daily basis, special attention is given to procedures designed for testing mice. While there has been no attempt to cover all areas of animal behavior and sensory pro- cessing, this text will help take the guesswork out of designing the methodology for many of the most widely used animal behavioral approaches developed for the study of brain disorders, drug abuse, toxicology, and cognitive drug development. One cautionary note to the newcomer to the behavioral field is to not be deceived by the manner in which this book presents its topics. As a matter of convenience, 0704/fm/frame Page vii Tuesday, July 18, 2000 11:10 AM © 2001 by CRC Press LLC the topics have been arranged in chapter form, and there may be the false sense of security that each method described is the last word on the subject. However, it is often not sufficient to employ one of these methods to assess the cognitive status of an animal. For example, when studying memory or recall, it is prudent to use a test battery that can better provide a comfortable level of interpretation of the effect of the perturbation applied to the subject. Spatial and non-spatial tasks should be considered. If a negative reinforcer is involved, such as electrical shock, the animal should be tested for his response to pain. Drugs or other manipulations that might alter pain sensitivity could give false impressions in a shock-motivated memory task. Drugs that affect motor activity may alter maze activity or swimming behavior, and drugs that alter taste, appetite, or that induce GI disturbances could affect food- motivated behaviors. Whenever possible, the animal should be observed (at least initially) while performing the task. It is often surprising to some investigators (this one included) to find that the animal is using a technique to solve the problem posed to it that was not considered in designing the task. A good example is the mediating or non- mnemonic strategies that rats use to solve matching problems in various operant paradigms. Most animals would rather use such strategies (such as orientating to a proffered lever) to obtain food rewards than to use memory. Whenever possible, our authors have provided some of these pitfalls in their chapters, although every possible contingency could not be anticipated. Thus, it is in the best interest of the investigator to use this book to help develop several strategies to understand the complex behav- iors of animals as they respond to drugs, new diets, surgical interventions, or to additional or fewer genes. While danger in anthropomorphizing the behavior of animals always exists, the investigator should feel some level of confidence that much of the behavioral literature is replete with instances of high predictive value for similar perturbations in humans. Of course, species and strain differences can limit such interpretations. Mice are clearly not little rats, and rats are not non-human primates. Each species has a specific level of predictive value that should be assessed. A final cautionary note is that investigators make every attempt to be as repro- ducible as possible when studying animal behavior. Handlers, experimenters, food, water, bedding, noise, surrounding visual cues, are just a few of the factors that should be held constant when performing behavioral studies. Inconsistency contrib- utes mightily to response variability in a population, and may even lead to a com- pletely opposite behavior to the one expected. At this point I would like to express my sincere thanks to the many authors who contributed these chapters. Their difficult task in preparing this information will make easier the tasks of our readers in their own efforts to assess animal behavior. I would also like to acknowledge the support (moral and technical) of the CRC staff, Publisher Barbara Norwitz, and Editorial Assistant Amy Ward, and the Methods in Neuroscience Series Editors, Sidney Simon and Miguel Nicolelis. Finally, I would like to thank my office administrator Vanessa Cherry for her many contributions in getting this book together for publication, and to my wife Regina Buccafusco, who is an education design specialist, for helping in the proofreading of the chapters. 0704/fm/frame Page viii Tuesday, July 18, 2000 11:10 AM © 2001 by CRC Press LLC The Editor Jerry J. Buccafusco, Ph.D. , is director of the Alzheimer’s Research Center, in the Department of Pharmacology and Toxicology of the Medical College of Georgia. He holds a joint appointment as Research Pharmacologist at the Department of Veterans Affairs Medical Center. He holds the rank of Professor of Pharmacology and Toxicology and Professor of Psychiatry and Health Behavior. Dr. Buccafusco was trained classically as a chemist, receiving an MS degree in inorganic chemistry from Canisius College in 1973. His pharmacological training was initiated at the University of Medicine and Dentistry of New Jersey where he received a Ph.D. degree in 1978. His doctoral thesis concerned the role of central cholinergic neurons in mediating a hypertensive state in rats. Part of this work included the measurement of several behavioral components of hypothalamically mediated escape behavior in this model. His postdoctoral experience included two years at the Roche Institute of Molecular Biology under the direction of Dr. Sydney Spector. In 1979 he joined the Department of Pharmacology and Toxicology of the Medical College of Georgia. In 1989 Dr. Buccafusco helped found and became the director of the Medical College of Georgia, Alzheimer’s Research Center. The Center hosts several core facilities, including the Animal Behavior Center, which houses over 30 young and aged rhesus monkeys who participate in cognitive research studies. Awards and honors resulting from Dr. Buccafusco’s research include the New Investigator Award, National Institute on Drug Abuse, 1980; Sandoz Distinguished Lecturer, 1983; Distinguished Faculty Award for the Basic Sciences, School of Medicine, Medical College of Georgia, 1988; Callaway Foundation of Georgia, Center Grant recipient, 1989; and the Distinguished Alumnus Award, University of Medicine and Dentistry of New Jersey, 1998. Dr. Buccafusco also served as a member of the Pharmacology II Study Section of the National Institute on Drug abuse from 1989–1991, and he is a member the Scientific Advisory Board of the Institute for the Study of Aging in New York. Dr. Buccafusco holds memberships in several scientific societies. In his profes- sional society, the American Society for Pharmacology and Experimental Therapeu- tics, he serves as Chairman of the Graduate Student Convocation subcommittee, and member of the Education Committee. He also serves as Associate Editor (Neuro-Behavioral Pharmacology section) of the Journal of Pharmacology and 0704/fm/frame Page ix Tuesday, July 18, 2000 11:10 AM © 2001 by CRC Press LLC Experimental Therapeutics . Finally, Dr. Buccafusco was an invited speaker and discussant at the National Institutes on Aging symposium on Age-Related Neurobe- havioral Research: An Integrative Cognitive Neuroscience Agenda for the 21st Cen- tury, held in 1999. Dr. Buccafusco’s research area includes the development of novel treatment modalities for Alzheimer’s disease and related disorders. In 1988 his laboratory was the first to report the cognitive enhancing action of low doses of nicotine in non- human primates. Since that time he has studied numerous novel memory-enhancing agents from several pharmacological classes in this model. His most recent work is directed at the development of single molecular entities that act on multiple CNS targets, not only to enhance cognitive function, but also to provide neuroprotection, or to alter the disposition and metabolism of amyloid precursor protein. Dr. Bucca- fusco also has studied the toxic effects of organophosphorus anticholinesterases used as insecticides and as chemical warfare agents. In particular, he has studied the behavioral/cognitive alterations associated with low level, chronic exposure to such agents. Finally, his work in the area of drug abuse has centered around the role of central cholinergic neurons in the development of physical dependence on opiates, and in the expression of withdrawal symptoms. These studies have been supported by continuous federally sponsored grants awarded by the National Institutes of Health, the Department of Defense, and the Veterans Administration. 0704/fm/frame Page x Tuesday, July 18, 2000 11:10 AM © 2001 by CRC Press LLC [...]... Strains F Tryon’s Maze-Bright and Maze-Dull Rats G Spontaneous Hypertensive Rats H Flinders Sensitive Line and Flinders Resistant Line I Dahl Salt Sensitive Rats © 20 01 by CRC Press LLC 1 0704/C 01/ frame Page 11 Monday, July 17 , 2000 4:35 PM Choice of Animal Subjects in Behavioral Analysis 11 VIII Comparison of Various Rat Strains for Behavioral Characteristics From the preceding sections, it is clear... Tuesday, July 18 , 2000 11 :10 AM Chapter 10 Spatial Navigational (Water Maze) Tasks Alvin V Terry, Jr Chapter 11 The Delayed Non-Match-to-Sample Radial Arm Maze Task: Application to Models of Alzheimer’s Disease Carl A Boast, Thomas J Walsh, and Adam C Bartolomeo Chapter 12 Use of the Radial-Arm Maze to Assess Learning and Memory in Rodents Edward D Levin Chapter 13 An Operant Analysis of Fronto-Striatal... Young, Ph.D Department of Medicinal Chemistry School of Pharmacy Virginia Commonwealth University Richmond, VA 0704/fm/frame Page xiv Tuesday, July 18 , 2000 11 :10 AM © 20 01 by CRC Press LLC 0704/fm/frame Page xv Tuesday, July 18 , 2000 11 :10 AM Contents Chapter 1 Choice of Animal Subjects in Behavioral Analysis William J Jackson Chapter 2 The Behavioral Assessment of Sensorimotor Processes in the Mouse:... aggressive cage-rattling behavior in captive rhesus monkeys is a manifestation of the wild defensive posture In the Davis et al studies, the stump-tailed macaques (Macaca speciosa) spent most of their time presenting and grooming This preoccupation with presenting and grooming by the stump-tailed monkeys resulted in lower scores in the remaining behavioral categories The reports of Kling and Orbach 51 and Orbach... clear that the most common outbred, and certainly the inbred rat strains, differ in regard to important baseline behavioral characteristics Some years ago, Harringon29,3 0-3 7 and others presented behavioral standardization data for several outbred and inbred rat strains The behavioral comparisons included activity in both stabilimeters,30, 31 open-field38 and rotating wheels,39 free operant lever press levels,37... other species The Jackson Lab in Bar Harbor, Maine is a leader in the development of the laboratory mouse © 20 01 by CRC Press LLC 0704/C 01/ frame Page 12 Monday, July 17 , 2000 4:35 PM Methods of Behavior Analysis in Neuroscience 12 One of the first steps toward learning more about the relationship of behavior to the mouse genome will be behavioral comparisons of various strains The NIH has funded a multicenter... matching behavior either These species differences relate very much to the Transfer Index (TI) of Rumbaugh,45 a useful tool for comparing cognitive skills between species Pigeons, in fact, do not form concepts of matching-to-sameness, but instead form individual stimulus-response links that are not mediated by a matching concept There are numerous papers in the recent literature in which the titles indicate... Chapter 6 Intravenous Drug Self-Administration in Nonhuman Primates Leonard L Howell and Kristin M Wilcox Chapter 7 Assessing Attention in Rats Philip J Bushnell Chapter 8 Assessment of Distractibility in Non-Human Primates Performing a Delayed Matching-to-Sample Task Mark A Prendergast Chapter 9 Inhibitory Avoidance Behavior and Memory Assessment John H Graham and Jerry J Buccafusco © 20 01 by CRC Press... abandon several well-trained pig-tails because of extreme aggressiveness toward human handlers © 20 01 by CRC Press LLC 0704/C 01/ frame Page 16 Monday, July 17 , 2000 4:35 PM Methods of Behavior Analysis in Neuroscience 16 Cynomolgus or Crab-eating macaques (Macaca fasicularis) have become more popular as biomedical research subjects, as imported rhesus monkeys are difficult to obtain These animals have... Models Strain Selection A The Wistar Rat Colony B The Long-Evans Strain C Strains from Columbia University D Sprague-Dawley Rats E Holtzman Rats F N/Nih Rats G Wild Norway Rats Inbred Rat Strains Selected for Various Behavioral Traits A Rat Strains Selected for Preference of — and Sensitivity to —Alcohol B ACI Strain C Strains Bred for Various Serotonin Receptors D Roman Strain E Maudsley Strains F Tryon’s . 2000 616 .8 ′ 027—dc 21 0 0-0 39762 0704/fm/frame Page iv Tuesday, July 18 , 2000 11 :10 AM © 20 01 by CRC Press LLC Series Preface Our goal in creating the Methods & New Frontiers in Neuroscience. determined by the utility of these books. 0704/fm/frame Page v Tuesday, July 18 , 2000 11 :10 AM © 20 01 by CRC Press LLC 0704/fm/frame Page vi Tuesday, July 18 , 2000 11 :10 AM © 20 01 by CRC. Lab in Bar Harbor, Maine is a leader in the development of the laboratory mouse. 0704/C 01/ frame Page 11 Monday, July 17 , 2000 4:35 PM © 20 01 by CRC Press LLC 12 Methods of Behavior Analysis