Methods in drug abuse research dr barry d waterhouse, CRC press, 2003 scan

METHODS & NEW FRONTIERS IN NEUROSCIENCE Series Editors Sidney A Simon, Ph.D Miguel A.L Nicolelis, M.D., Ph.D Published Titles Apoptosis in Neurobiology Yusuf A Hannun, M.D., Professor of Biomedical Research and Chairman/Department of Biochemistry and Molecular Biology, Medical University of South Carolina Rose-Mary Boustany, M.D., tenured Associate Professor of Pediatrics and Neurobiology, Duke University Medical Center Methods for Neural Ensemble Recordings Miguel A.L Nicolelis, M.D., Ph.D., Professor of Neurobiology and Biomedical Engineering, Duke University Medical Center Methods of Behavioral Analysis in Neuroscience Jerry J Buccafusco, Ph.D., Alzheimer’s Research Center, Professor of Pharmacology and Toxicology, Professor of Psychiatry and Health Behavior, Medical College of Georgia Neural Prostheses for Restoration of Sensory and Motor Function John K Chapin, Ph.D., Professor of Physiology and Pharmacology, State University of New York Health Science Center Karen A Moxon, Ph.D., Assistant Professor/School of Biomedical Engineering, Science, and Health Systems, Drexel University Computational Neuroscience: Realistic Modeling for Experimentalists Eric DeSchutter, M.D., Ph.D., Professor/Department of Medicine, University of Antwerp Methods in Pain Research Lawrence Kruger, Ph.D., Professor or Neurobiology (Emeritus), UCLA School of Medicine and Brain Research Institute Motor Neurobiology of the Spinal Cord Timothy C Cope, Ph.D., Professor of Physiology, Emory University School of Medicine Nicotinic Receptors in the Nervous System Edward D Levin, Ph.D., Associate Professor/Department of Psychiatry and Pharmacology and Molecular Cancer Biology and Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine Methods in Genomic Neuroscience Helmin R Chin, Ph.D., Genetics Research Branch, NIMH, NIH Steven O Moldin, Ph.D, Genetics Research Branch, NIMH, NIH Methods in Chemosensory Research Sidney A Simon, Ph.D., Professor of Neurobiology, Biomedical Engineering, and Anesthesiology, Duke University Miguel A.L Nicolelis, M.D., Ph.D., Professor of Neurobiology and Biomedical Engineering, Duke University The Somatosensory System: Deciphering the Brain’s Own Body Image Randall J Nelson, Ph.D., Professor of Anatomy and Neurobiology, University of Tennessee Health Sciences Center New Concepts in Cerebral Ischemia Rick C S Lin, Ph.D., Professor of Anatomy, University of Mississippi Medical Center DNA Arrays: Technologies and Experimental Strategies Elena Grigorenko, Ph.D., Technology Development Group, Millennium Pharmaceuticals Methods for Alcohol-Related Neuroscience Research Yuan Liu, Ph.D., National Institute of Neurological Disorders and Stroke, National Institutes of Health David M Lovinger, Ph.D., Laboratory of Integrative Neuroscience, NIAAA In Vivo Optical Imaging of Brain Function Ron Frostig, Ph.D., Associate Professor/Department of Psychobiology, University of California, Irvine Primate Audition: Behavior and Neurobiology Asif A Ghazanfar, Ph.D., Primate Cognitive Neuroscience Lab, Harvard University 2345_frame_FM Page Wednesday, October 23, 2002 2:16 PM Library of Congress Cataloging-in-Publication Data Methods in drug abuse research : cellular and circuit level analyses / edited by Barry D Waterhouse p cm (Methods & new frontiers in neuroscience) Includes bibliographical references and index ISBN 0-8493-2345-2 (alk paper) Drugs of abuse Research Methodology Drug abuse Research Methodology Neurons Neural circuitry I Waterhouse, Barry D II Methods & new frontiers in neuroscience series RM316 M48 2002 615¢.78¢072 dc21 2002074127 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 authors 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 $1.50 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 0-8493-2345-2/03/$0.00+$1.50 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 Visit the CRC Press Web site at www.crcpress.com © 2003 by CRC Press LLC No claim to original U.S Government works International Standard Book Number 0-8493-2345-2 Library of Congress Card Number 2002074127 Printed in the United States of America Printed on acid-free paper 2345_frame_FM Page Wednesday, October 23, 2002 3:20 PM 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 cover topics ranging from methods to investigate apoptosis, to modern techniques for neural ensemble recordings in behaving animals The series also covers new and exciting multidisciplinary areas of brain research, such as computational neuroscience and neuroengineering, and describes breakthroughs in classical fields like behavioral neuroscience We want these books 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 Each book is edited by an expert and consists of chapters written by the leaders in a particular field Books are richly illustrated and contain comprehensive bibliographies Chapters provide substantial background material relevant to the particular subject Hence, they are not only “ methods books,” but they also contain detailed “tricks of the trade” and information as to where these methods can be safely applied In addition, they include information about where to buy equipment and about web sites helpful in solving both practical and theoretical problems We hope that as the volumes become available, the effort put in by us, by the publisher, by the book editors, and by 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 Sidney A Simon, Ph.D Miguel A.L Nicolelis, M.D., Ph.D Series Editors 2345_frame_FM Page Wednesday, October 23, 2002 2:16 PM 2345_frame_FM Page Wednesday, October 23, 2002 2:16 PM Dedication To Kathy for her unwavering love, companionship, and support through all my scientific endeavors 2345_frame_FM Page Wednesday, October 23, 2002 2:16 PM 2345_frame_FM Page Wednesday, October 23, 2002 2:16 PM About the Editor Barry D Waterhouse is a professor in the Department of Neurobiology and Anatomy and an associate dean of biomedical graduate studies at Drexel University College of Medicine (formerly MCP-Hahnemann University School of Medicine) After receiving his B.S degree in biology in 1971 from Muhlenberg College, Dr Waterhouse completed his Ph.D in pharmacology at Temple University in 1977 From 1977 through 1987 he worked at Southwestern Medical School, University of Texas at Dallas, rising from postdoctoral fellow, to instructor, and then finally to assistant professor In 1987 he was recruited to the Department of Physiology and Biophysics as an associate professor at Hahnemann University School of Medicine, where in 1988 he developed and was subsequently appointed director of the university's graduate program in neuroscience, a post he held until 1994 In 1992 he was promoted to professor of physiology and biophysics, and in 1994, when Hahnemann University merged with Medical College of Pennsylvania (MCP), Dr Waterhouse was invited to join the Department of Neurobiology and Anatomy in the newly formed university He continued as director of the neuroscience graduate program at MCP-Hahnemann until 2001 and also served as vice-chair of the Department of Neurobiology and Anatomy from 1999 to the present He was elected to the American College of Neuropsychopharmacology in 1996 and to the College on Problems of Drug Dependence in 1995 Throughout his research career Dr Waterhouse has focused on the neurobiology of central monoaminergic systems and psychostimulant drug actions 2345_frame_MASTER.book Page 269 Wednesday, October 23, 2002 1:03 PM Pharmacological Investigations of Neural Mechanisms 269 76 Randrup, A and Munkvad, I., Role of catecholamines in the amphetamine excitation response, Nature, 211, 540,1966 77 Risner, M.E and Jones, B.E., Role of noradrenergic and dopaminergic processes in amphetamine self-administration, Pharmacol Biochem Behav., 5, 477, 1976 78 Robinson, T.E., Castañeda, E., and Whishaw, I.Q., Compensatory changes in striatal dopamine neurons following recovery from injury induced by 6-OHDA or methamphetamine: a review of evidence from microdialysis studies, Can J Psychol., 44, 253, 1990 79 Rolinski, Z and Scheel-Kruger, J., The effect of dopamine and noradrenaline antagonists on amphetamine induced locomotor activity in mice and rats, Acta Pharmacol Toxicol., 33, 385, 1973 80 Roth, R.H., Murrin, C.L., and Walters, J.R., Central dopaminergic neurons: effects of alterations in impulse flow on the accumulation of dihydroxyphenylacetic acid, Eur J Pharmacol., 36, 163, 1976 81 Sherin, J.E., Shiromani, P.J., McCarley, R.W., and Saper, C.B., Activation of ventrolateral preoptic neurons during sleep, Science, 271, 216, 1996 82 Skolnick, P., Stalvey, L.P., Daly, J.W., Hoyler, E., and Davis, J.N., Binding of alpha and beta adrenergic ligands to cerebral cortical membranes Effect of 6-hydroxydopamine treatment and relationship to the responsiveness of cyclic AMP generating systems in two rat strains, Eur J Pharmacol., 47, 201, 1978 83 Smythe, J.W., Christie, B.R., Colom, L.V., Lawson, V.H., and Bland, B.H., Hippocampal theta field activity and theta-on/theta-off cell discharges are controlled by an ascending hypothalamo-septal pathway, J Neurosci., 11, 2241, 1991 84 Snoddy, A.M and Tessel, R.E., Prazosin: effect on psychomotor-stimulant cues and locomotor activity in mice, Eur J Pharmacol., 116, 221, 1985 85 Sporn, J.R., Wolfe, B.B., Harden, T.K., Kendall, T., and Molinoff, P.B., Supersensitivity in rat cerebral cortex: pre-and post-synaptic effects of 6-hydroxydopamine at noradrenergic synapses, Mol Pharmacol., 13, 1170, 1977 86 Steriade, M and Buzsaki, G., Parallel activation of thalamic and cortical neurons by brainstem and basal forebrain cholinergic systems, in Brain Cholinergic Systems, Steriade, D and Biesold, M., Eds., Oxford University Press, Oxford, 1990, pp 3–62 87 Steriade, M and McCarley, R.W., Brainstem Control of Wakefulness and Sleep, Plenum Press, New York, NY, 1990 88 Steriade, M., Jones, E.G., and Llinas, R.R., Thalamic Oscillations and Signaling, Wiley-Interscience, New York, NY, 1990 89 Swanson, L.W and Hartman, B.K., The central adrenergic system: an immunoflourescence study of the location of cell bodies and their efferent connections in the rat utilizing dopamine-b-hydroxylase as a marker, J Comp Neuroanat 163, 467, 1975 90 Swanson, L.W., Brain Maps: Structure of the Rat Brain, Elsevier, Amsterdam, 1992 91 Timo-Iaria, C., Negrao, N., Schmidek, W.R., Hoshino, K., de Menezes Lobato, C.E., and Da Rocha, T.L., Phases and states of sleep in the rat, Physiol Behav., 5, 1057, 1970 92 Tyler, T.D and Tesel, R.E., Norepinephrine uptake inhibitors as biochemically and behaviorally selective antagonists of the locomotor stimulation induced by indirectly acting sympathomimetic amines in mice, Psychopharmacology, 69, 27, 1980 93 Valentino, R.J., Page, M.E., and Curtis, A.L., Activation of noradrenergic locus coeruleus neurons by hemodynamic stress is due to local release of corticotropinreleasing factor, Brain Res., 555, 25, 1991 94 Vanderwolf, C.H and Robinson, T.E., Reticulo-cortical activity and behavior: a critique of the arousal theory and a new synthesis, Behav Brain Sci., 4, 459, 1981 2345_frame_MASTER.book Page 270 Wednesday, October 23, 2002 1:03 PM 270 Methods in Drug Abuse Research: Cellular and Circuit Level Analyses 95 Waterhouse, B.D., Moises, H.C., Yeh, H.H., and Woodward, D.J., Norepinephrine enhancement of inhibitory synaptic mechanisms in cerebellum and cerebral cortex: mediation by beta adrenergic receptors, J Pharmacol Exp Ther., 221, 495, 1982 96 Waterhouse, B.D., Sessler, F.M., Cheng, J.T., Woodward, D.J., Azizi, S.A., and Moises, H.C., New evidence for a gating action of norepinephrine in central neuronal circuits of mammalian brain, Brain Res Bull., 21, 425, 1988 97 Wise, R.A and Bozarth, M.A., Brain mechanisms of drug reward and euphoria, Psychiatr Med., 94, 469, 1987 98 Zaborsky, L., Afferent connections of the forebrain cholinergic projection neurons, with special reference to monoaminergic and peptidergic fibers, in Central Cholinergic Synaptic Transmission, Frotscher, M and Misgeld, U., Eds., Birkhauser Verlag, Boston, 1989 2345_frame_IDX Page 271 Tuesday, October 29, 2002 10:58 AM Index A Accumbal activity chronic extracellular recordings of, 162 firing patterns of, 184 inhibitory effects of cocaine on, 190 in stimulus-reward learning, 188 Accumbal recording studies, 179 See also Chronic extracellular recording Acquisition of drug self-administration See also Self-administration factors attenuating, 27 studies, 18, 28 Addiction, drug See also Reinforcement cellular aspects of, 5–6 characteristics of, and cortical abnormalities, genetic predisposition to, incentive motivation theories of, 164–165 neural mechanisms of, stages of, 195 theories of, 2–5 Addictive behavior, neurobiological basis for, 158 See also Behavior Airflyte counterbalance, 197, 200 Alcohol, neuroadaptive changes in brain produced by, 78 Allostasis, principle of, American Association of the Accreditation of Laboratory Animal Care (AAALAC), 58 Amperometric detector, LC–4C, 70 Amperometry, 93 See also High-speed chronoamperometry d-amphetamine and Purkinje neuron responses, 124 voltammetric study of, 102 Amphetamine (AMPH)-like stimulant drugs, 240 arousal-enhancing actions of, 243, 263 arousal induced by, 258–263 basal forebrain and, 260–262 in vivo neurochemistry, 247 NE-dependent behavioral actions of, 245 wake-promoting actions of, 252 Amphetamines behavior reinforcing aspects of, 119, 120 in vivo microdialysis study of, 52–53 monoaminergic effects of, 120 sensory-information processing affected by, 121 Anesthesia halothane, 247–249 for in vivo microdialysis, 58, 59, 64 for jugular catheterization, 202–203 membrane properties influenced by, Anesthetics, topical, 146 Animal models catheterization procedure in, 38–42 in chronic extracellular recording technique, 168 cricket, 215 for drug seeking, 163 halothane-anesthetized, 247–249, 255, 262–263, 264 of human drug addiction, Long-Evans rats, 167 nonhuman primate, 215 rodent trigeminal somatosensory system, 125, 229 voltammetric techniques used with, 100–101 whole-animal preparations, 112–114 Anterior cingulate cortex (ACC), Antibodies, in self-administration studies, 27 Apparatus See also Instrumentation for in vivo probe-recovery experiment, 56 for self-administration studies, 33–38 Area-under-the-curve (AUC), in microdialysis analysis, 72 Arousal, AMPH-induced involvement of NA ß-receptors in, 262–263, 264 and LC-NA system, 253–263 and role of norepinephrine, 258–259 Arousal, defined, 241 Arousal, stimulant-induced, 240 neurobiology of, 243–247 procedures for assessment of, 247–253 Artificial cerebrospinal fluid (aCSF), 65 Artificial cerebrospinal fluid (aCSF) perfusion medium, 62, 63, 74 Autoinjectors, 72 Autoradiography, to assess diffusion, 244 Axon Instruments, Inc., 95–96 271 2345_frame_IDX Page 272 Tuesday, October 29, 2002 10:58 AM 272 Methods in Drug Abuse Research: Cellular and Circuit Level Analyses B “Barrel field,” 215 Behavior See also Addiction cocaine-maintained, 30 experimental analysis of, 25 neuronal activity and, 144 neuropharmacology of, 244, 245 and specific drug actions, 166 Behavior, drug-related, animal models for, mechanisms mediating, patterns of, 179 responding, 20–21 variables affecting, 23 Bethanechol, radius of action for, 246 Biographics, Inc., 147 Brain drug effects on, extracellular fluid (ECF) of, 55 neurochemistry of, 52 in whole animal preparations, 113 Brain slices, voltammetric recording techniques for, 98–100 Brain stress systems, and drug addiction, Break point, in self-administration studies, 32–33 Buprenorphine, as replacement compound, 27 Bupropion, as replacement compound, 27 C Caffeine, in self-administration studies, 23, 24 Calcium, endogenous neurotransmitters affected by, 55 Cannabinoids, voltammetric study of, 104 Cannula, intracranial guide, 60–62 Carbon fiber “working” microelectrodes, 90–91 Catecholamines and AMPH-induced behavior, 244–246 in dialysate sample, 70 lesion-induced responses in, 244 voltammetric study of, 101 Catheter in chronic extracellular recording, 196 in self-administration studies, 35–38 Catheter, in-dwelling jugular, 58–59 post-surgical maintenance of, 60 preparation of, 59 surgical implantation of, 59–60 Catheterization procedure, for rats, 38–42 Cells in culture, voltammetric study of, 97–98 See also Voltammetry Ceramic-based sensors, 91 Cerebellum, effect of psychostimulants on, 122–125 Cerebrospinal fluid, artificial (aCSF), 65 Chem-Clamp, 96 Cholinergic agonist, radius of action for, 246 Chromatogram, in microdialysis analysis, 72 Chronic extracellular recording anatomical resolution of, 164 chronically implanted vs movable electrodes in, 163–164 drug effect vs behavioral feedback, 165 incentive motivation theories in, 164–165 i.v drug self-administration in, 163 of mechanisms of drug action, 166–167 of multiple drug effects, 166 rationale for, 162–163 temporal range of, 164–165 Chronic extracellular recording technique for acute drug effects, 184–189 applications of, 178–179 electrophysiological recording session, 169 firing patterns in, 175–178 histological analyses in, 192–194, 204–205 incentive-related information encoding, 179–184 instrumentation for, 195, 196–202 methods, 167–169 post-operative care for, 203–204 for repeated self-administration, 190–192 research in, 194–195 surgical procedures in, 202–203 utility of, 167 Chronoamperometry, high-speed, 93–94, 99 Clamping procedure in chronic extracellular recording, 186, 187–188 in neurophysiological investigation, 165 Clearance kinetics, 88 Clonidine, neuronal computation altered by, 232 Coatings electrode, 91–92 electropolymerized, 92 Cocaine, 120 alterations in sensory experience with, 132 behavior reinforcing aspects of, 119 differential effects of, 230 drug delivery study of, 26, 27 effect on cortical neurons of, 127–129 effect on dopamine of, 76 effects on neuronal function, 113 effects on thalamic neurons, 129–132 and GABA iontophoretic pulses, 123–124 lethality associated with, 26 neurobiological effects of, 82 perceptual processes affected by, 214–215 2345_frame_IDX Page 273 Tuesday, October 29, 2002 10:58 AM Index pharmacological effects of, 189 reinforcing properties of, 25, 30, 31 in self-administration studies, 19, 23, 29–31 sensory cortical neuron responses augmented by, 126 sensory-information processing affected by, 121 Cocaine studies accumbal role in, 189–190 in vivo microdialysis, 52–53 incentive-related information-encoding in, 179–184 systemic administration in, 231 voltammetric, 98, 103 Co-eluting peaks, problem of, 75 Computerization, of microdialysis, 72 See also Software Connectivity in dose-response studies, functional, 228–229, 232 Contingent relationship, in self-administration studies, 25–27 Cortex abnormalities in addicted individuals, effect of cocaine on, 127–129 effects of psychostimulants on, 125 orbitofrontal, Crash phase, of stimulant withdrawal, 78 Cross-correlation analysis, of single-neuron spike trains, 228–229, 232 Cross-correlation histograms (CCH), in multineuron recording system, 228 Crosscorrelograms, event-related, 155 Cyclic voltammetry, 94–95 Cypress Systems, 96 Cytoarchitecture, in dose-response studies, D Dagan Corp., 96 Data, electrophysiological, 169–175 See also Electrophysiological studies Data-acquisition software, for many-neuron recording technique, 147–148 See also Software Data-analysis systems, computerized chromatographic, 72 DataWave Technologies Corp., 169, 170 Delay discounting, 42 Detector, electrochemical, 70 Dialysate sample assaying, 74–75 neurotransmitter concentration in, 72 obtaining, 69 273 recovery in, 55–56 Dialysis membrane action of, 63 properties of, 54 Diffusion drug, 246 microdialysis, 53–55 voltammetric study of, 97–98 3,4-dihydroxyphenylacetic acid (DOPAC), standards for, 73 Discriminant analysis, ensemble neuronal data for, 155 Discrimination procedures, in waveform analysis, 171 Dopamine (DA), 27 and actions of AMPH-like stimulants, 245 and AMPH-induced locomotor activity and stereotypy, 247 detection of, 52, 53 detection of sub-pg amounts of, 70–71 in dialysate sample, 77 in drug addiction, 75 effects of cocaine on, 103 effects of methamphetamine on, 77, 78 effects of stimulant drugs on, 77, 120 electrically evoked release of, 97, 98 impact of AMPH on, 240–241 methamphetamine-evoked release of, 80 in microdialysis, 54 standard curves for, 73 voltammetric measure of, 96, 101 Dopamine transporter (DAT) proteins, 102 in medication of addiction, 79–80 and stimulant drugs, 76 Dopaminergic systems and arousal-enhancing actions of AMPH-like stimulants, 264 effects of chronic d-amphetamine treatment on, 102 Dose, in experimental design, 243 Dose-effect curve, downward turn of, 31 Dose-response curves for cocaine self-administration, 19, 20 for heroin self-administration, 21 and multiple drug effects, 166 Dose-response relationships, cellular experiments in, Drug abuse and liability, 42 over time, 232 voltammetric study of, 101–104 Drug action, receptor mechanisms of, Drug administration, contingent vs noncontingent, 25–27 See also Selfadministration 2345_frame_IDX Page 274 Tuesday, October 29, 2002 10:58 AM 274 Methods in Drug Abuse Research: Cellular and Circuit Level Analyses Drug craving, neurobiological basis of, 120 Drug delivery, response-dependent vs -independent, 26 Drug effects and accumbal information processing, 188–189 vs behavioral feedback, 165, 185–188 dose-dependent firing rate, 184–185, 186 mediated by nucleus accumbens, 75–76 mirroring changes in drug level, 184, 185, 186 multiple, 166 of repeated self-administration, 190–192 on sensory signal processing, 119 (See also Amphetamine-like stimulant drugs; Stimulant drugs) wake-promoting actions, 251 Drug seeking, animal models in study of, 163 in chronic recording studies, 195 and motivational processing, 188 neural basis of, 212 neural encoding controlling Drugs of abuse, cellular techniques in study of, 8–9 E E-Chempro electrochemical instrument, 96 Economics, behavioral, 42 EI–400, 96 Electrical stimulation effect of cocaine on, 126–127 as reinforcer, 25 Electrochemical detector, in microdialysis, 70, 71 See also High-performance liquid chromatography Electrodes See also Microelectrodes auxiliary, 93 for many-neuron recording technique, 144–145 reference, 92–93 stimulating, 217–218 used in voltammetry, 90–93 Electroencephalogram (EEG) recordings in arousal studies, 241–242 of drug-related behavior, of forebrain, 247–248 NA-dependent alterations in, 246 of sleep-wake states, 249–250 Electromyogram (EMG) recordings, of sleepwake states, 249–250 Electronic harness, in chronic extracellular recording, 198, 199 Electrophysiological recording, multichannel, 143 See also Many-neuron recording technique Electrophysiological studies equipment for, 201–202 for evaluating psychostimulant actions, 122–132 in intact animals, 113 ISI analysis of, 171–175 specific receptor agonists and antagonists in, 166 waveform analysis, 169–171 Electrophysiological techniques background of, 119 for central monoaminergic systems, 120–121 for sensory-signal processing, 121 Environment and drug-related behavior, 20–21 as reinforcer, 25 Enzymes, as electrode coatings, 92 EPOCH analysis function, 224–227, 229 Ethanol, voltammetric study of, 101 Evoked discharges, drug-induced changes in, 117–118 Extracellular fluid (ECF) See also Dialysate sample continuous sampling of, 52 in microdialysis, 54 neuronal, 55 neurotransmitter concentration in, 57 Extracellular recording, 118 F Factor analysis, in spike train activity, 229–230 FAST–12 instrument, 96 Fast-scan cyclic voltammetry (FCV), 94 Feed-forward cycle, drug addiction as, FEP tubing, 63, 64 Field effect transistors (FETs), 147, 201 Firing patterns and dose-dependent changes in, 184–185, 186 and drug effect vs behavioral feedback, 185–188 and drug reward expectation, 184 and drug taking, 193 group mean neural data for, 178 individual neuron data in, 175–178 information encoding with lever-press, 180 in ISI analysis, 172, 173 mirroring changes in drug level, 184, 185, 186 misrepresentative, 173 and motivational processing, 188 and multiple drug effects, 166 2345_frame_IDX Page 275 Tuesday, October 29, 2002 10:58 AM Index time-locked to cocaine, 179–180, 181 Firing rates, in factor analysis, 227 Fixed-interval (FI) schedule, in drug selfadministration studies, 33 Fixed-ratio (FR) schedules, in self-administration studies, 22, 29–31 Flow cell compartment, in microdialysis, 68–70 Flush procedures, for in-dwelling jugular catheter, 60 Food restriction, in self-administration studies, 23, 25 Forebrain activity state of, 253–255 during arousal, 242, 260–262 EEG measurement of, 247–248 Functional connectivity, in spike train activity, 228–229, 232 275 High-performance liquid chromatography (HPLC), 52, 66 High-performance liquid chromatography with EC detector (HPLC-EC system), 66, 67, 77 for detection of monoamine transmitters, 65 and dialysate sample, 74–75 High-speed chronoamperometry (HSC) recordings, 93–94, 95, 99 Hippocampus, 100 History, behavioral and drug, 21–25 Homovanillic acid (HVA), standards for, 73 Housing chambers, in self-administration studies, 34–35, 37 See also Testing chamber HPLC pumps, 68, 72 5-hydroxyindoleacetic acid (5-HIAA), standards for, 73 Hypothalamo-pituitary-adrenal (HPA) axis, in self-administration studies, 23 G Gain-amplifying effects, of drug addiction, Gamma-amino butyric acid (GABA), 122 cerebellar Purkinje cell response to, 122 in chronic drug administration, 134 iontophoretic delivery of, 123 GBR 12909 (dopamine (DA) uptake blocker), 79–80 GBR-decanoate, 80–82 GBR-hydroxy, 80, 81 Gene Clamp 500, 96 Genetic predisposition, to drug addiction, Genetics, behavioral, 42 L-glutamate, voltammetry study of, 96–97 Glutamate application, effect of cocaine on, 126–127 GMA Technologies, Inc., 96 Guide cannula, for in vivo microdialysis, 60–62 H Halothane-anesthetized animals AMPH-induced EEG activation in, 262–263, 264 isoproterenol infusion of, 255 pharmacological manipulations in, 247–249 Harm reduction, 27 Harness, electronic, 198, 199 Headset, microwire array, 197–198 Hedonic dysregulation theory, experimental approaches in, weakened cortical inhibitory mechanisms in, Heroin, in self-administration studies, 19–20 I Imaging studies, of brain, Implantation of jugular catheter, 58–60 of microelectrode arrays, 145 Impulsivity, models of, 42 In vivo measurements, 163 Incentive motivation theories, of addiction, 2–3, 164–165 Incentive-related information encoding, 179–184 Indoleamines, in dialysate sample, 70 Information, digital, 158 See also Software Information encoding incentive-related, 179 with lever-press patterns, 180 Inhibition, effect of addictive drugs on, 189 Instrumentation for chronic extracellular recording, 195, 196–202 for in vivo microdialysis, 67–70 for in vivo voltammetric recordings, 88, 89 for multineuron recording system, 218, 220–221 for voltammetric studies, 95–96 Interspike-interval (ISI) histograms defined, 171 examples, 172, 174 limitations of, 175 minimum, 171–172 single-neuron data on, 173, 174 Intracerebral infusions, wake-promoting actions of, 251–252 Intracerebral ventricular (ICV) infusions, 249 2345_frame_IDX Page 276 Tuesday, October 29, 2002 10:58 AM 276 Methods in Drug Abuse Research: Cellular and Circuit Level Analyses Intracranial guide cannula, for in vivo microdialysis, 60–62 Intracranial self-stimulation (ICSS), and withdrawal, Intramural Research Program (IRP), 58 Intratissue infusions, 249 Intravenous drug delivery automatic, 17–18 methodological advantages of, 18 Intravenous-drug self-administration model, ISCO 260D pump, 68, 69 Isoproterenol, EEG effects of, 256, 257 J Jugular catheter, implantation of, 58–60 Jugular catheterization, in chronic extracellular recording, 202 L Learning drug effects of, 193 drug-induced amplification of, 2–3 Lemniscal pathway, 217 Lesion studies, of AMPH-induced behavior, 244 Liability, abuse, 42 Liquid chromatography, high-performance, 52, 66 Locomotion, in chronic extracellular recording, 186, 187 Locus coeruleus (LC), properties of, 253 Locus coeruleus (LC)-NA system and arousal, 253–256 and arousal-enhancing actions, 241 Locus coeruleus-norepinephrine (LC-NE) system and forebrain activity, 258–259 and thalamocortical neuron function, 226, 227, 232 Long-Evans rats, 167 M Maintenance of drug self-administration factors attenuating, 27 studies, 18, 29 Mann-Whitney test, 175 Many-neuron electrophysiology, 144 Many-neuron recording technique advances in, 157 advantages of, 144 chronic implants in, 145–146 electrodes in, 144–145 in vivo, 143 microwire array, 148 procedures, 146–148 stability of, 150, 151 yields from, 149–150 Mapping studies, 246, 248 Marijuana, voltammetric study of, 104 Matlab, 224, 226, 227, 228 MED Associates Inc., 202 Medial preoptic area (MPOA), in sleep/wake studies, 255, 256, 260 Medications, development of, 79–82 Methadone, as replacement compound, 27 Methamphetamine effects on dopamine of, 76, 78 effects on serotonin of, 79 5-HT release induced by, 80 neurotoxicity of, 82 Methohexital (Brevital sodium), for anesthesia, 64 Methylphenidate, NE-releasing actions of, 243 Microdialysis, in alterations in monoamine neurotransmission, 246–247 chemical interaction in, 66 compared with voltammetric technique, 88 methods, 62–66 quantitative methods to, 78 in research, 82 running experiments, 65 testing chamber, 60 voltammetry compared with, 95 Microdialysis, in vivo, 52 advantages of, 58 analytical methods, 66-75 in awake animals, 64-65 basic principles of, 53-58 catheter implantation for, 58-60 data acquisition and analysis in, 71-75 intracranial guide cannula implantation for, 60-62 mobile phase conditions, 70-71 probe/tissue interactions in, 57-58 technique, 63-64 workstation, 67 Microelectrode arrays, chronic implants of, 145146 Microelectrodes See also Electrodes carbon fiber "working," 90-91 coatings for, 91-92 for voltammetry, 89-90, 91 Microinfusion techniques, 245-246 Microinjection pump, CMA 100, 63 Microiontophoresis, 114-115 Micropressure-ejection techniques, 114 Microwire array headset, 197-198 Microwire electrode arrays, 145 2345_frame_IDX Page 277 Tuesday, October 29, 2002 10:58 AM Index Midazolam, drug delivery study of, 27 Millar Voltammeter, 96 Millenium Chromatography Manager, 72 MK-801, 23 Molecular biology, 5, 42, 76 Monoamine mix standard, 73 Monoamine neurotransmitters effects of stimulant drugs on, 120 in vivo microdialysis assessment of, 246-247 in solute recovery, 55 wake-promoting actions of, 243 Morphine, response-dependent administration of, 26 See also Opiates Mothers, studies in offspring of drug-addicted, Motivation, 188 and drug-seeking, 188 opponent process theory of, Multichannel Acquisition Processor (MAP) hardware, 218, 220, 221 Multichannel recording approach advantages of, 231, 232 research in, 233 Multineuron recording system apparatus for, 220 components of, 218, 220-221 experimental session in, 221 multiunit spike train activity in, 224-230 offline validation single-neuron recording in, 222-224 online spike sorting in, 221-222 perievent stimulus histograms in, 219 waveform discrimination in, 221-224 Multiunit recording experiments, 231 single-cell recording studies confirmed by, 231 N Nafion coating, 92, 95, 97 National Institute on Drug Abuse (NIDA), 58 NB Labs, 145 Nervous system, effect of chronic drug addiction on, Neural activity, extracellular recording of, 222 Neural firing, and drug administration, 167 See also Firing patterns Neurobiology of drug abuse, 143 of stimulant-induced arousal, 243-247 Neurochemistry brain, 52 of drug-related behavior, of stimulant drug withdrawal, 78 277 of stimulant drugs, 53 NeuroExplorer software, 148, 224 Neuromodulators, voltammetric study of, 97 Neuron discharge patterns, multichannel recording strategies for, 232 Neuronal activity, PC representation of, 229-230, 232 Neuronal ensemble data, 154-157, 158 Neuronal pairs, in spike train analysis, 152-154 Neurons See also Firing patterns; Single neurons in dose-response studies, 6-7 in drug-related behavior, functional connectivity of, 228-229, 232 Neurophysiology behavioral, 158 chronic vs acute approach to, 164 of drug effect vs behavioral feedback, 165 of drug-related behavior, Neuroplasticity, drug-induced, Neuroscience, experimental methods in, Neurotoxins, vulnerability to, 79 Neurotransmission effects of enhancing, 243 effects of stimulants on, 75 monoamine, 53 Neurotransmitter release, stimulant-induced alterations in, 246-247 Neurotransmitters detection of, 52, 53, 72-73 in dialysate sample, 74 exocytotic release of, 55 for maintenance of alert waking, 252-253 microelectrode response for, 90 release, 88 voltammetric study of, 96-97, 104 wake-promoting actions of, 251 Nex analysis scripts, 226, 227 Nicotine as reinforcer, 25 in self-administration studies, 23 NO, voltammetry study of, 96 Norepinephrine (NE) and alterations in blood pressure, 245 and AMPH-induced increases in arousal, 259, 260 and AMPH-induced locomotor activity and stereotypy, 247 and arousal-enhancing action of drugs, 258263 and arousal state, 255-256 behavioral/cognitive functions within SI of, 256 in chronic drug administration, 134 detection of, 52, 53 detection of sub-pg amounts of, 70-71 2345_frame_IDX Page 278 Tuesday, October 29, 2002 10:58 AM 278 Methods in Drug Abuse Research: Cellular and Circuit Level Analyses effect of cocaine on, 131 effects of stimulant drugs on, 77, 120 impact of AMPH on transmission of, 240-241 and increased arousal, 255-257 and maintenance of alert waking, 258 and sensory-signal processing, 121-122 voltammetric measures of, 96 Nucleus accumbens See also Accumbal activity drug effects mediated by, 75-76, 77 histological analyses of, 192-194 O Operant chambers See also Testing chamber in chronic extracellular recording studies, 168, 200-201 Plexiglas, 167, 168 in self-administration studies, 33-34 Operational Amplifiers (Op-Amps), 147 Opiates neuroadaptive changes in brain produced by, 78 self-administration studies of, 19 Opponent process theory, of motivation, Orbitofrontal cortex, P Paralemniscal pathway, 216 Patch clamp studies, 132 P.D Systems, 96 Perception, effects of cocaine on, 226 Perfusion fluid, in microdialysis, 55, 62-63 Perfusion system dead volume of, 65 total volume of, 66 Peristimulus time histogram (PSTH) in cocaine studies, 229, 230 in spike train activity, 224 Persistence of drug-induced changes and drug-related behavior, 20 physiological bases for, 132 Pharmacological agents, as reinforcers, 25 Pharmacological probes, microinjection of, 167 Phencyclidine lethal effects associated with, 26 self-administration of, 23 Physiology, of drug abuse, See also Neurophysiology Piezoelectric bimorph stimulator, 130 Plexon, Inc., 147 Polyethylene glycol coating, 145-146 Population data, in spike train activity, 228 Post-reinforcement pause (PRP), 30 Post-stimulus time histograms (PSTHs), 115, 116, 118, 129 Potentiostats, 95-96, 101 Power-spectrum analyses (PSA), 249, 250 Prazosin, impact on arousal of, 258, 259 Principal component (PC) analysis, 229-230, 232 eigenfunctions generated by, 232-233 of spike-train activity, 229-230, 232 Probe-recovery experiment, 56-57 Probes, in microdialysis, 53-55, 62 Probe/tissue interactions, in microdialysis, 57-58 Progressive-ratio schedules, in self-administration studies, 22, 31-33 Psychoactive substances actions on neural network functions of, 214 and sensory signal processing, 231 Psychomotor stimulants See Stimulant drugs Psychostimulant drugs See also Stimulant drugs behavior-reinforcing aspects of, 119 effects on central monoaminergic systems of, 120-121 monoamine cell discharge suppressed by, 122 in monoaminergically innervated brain circuits, 122-126 physiological actions of, 124-125 Pub Med database, 52 Pumps for drug infusions, 36 HPLC, 68 for in vivo microdialysis, 68 microinjection, 63 Purkinje cells in chronic drug administration, 134 in patch-clamp studies, 132 Q Quanteon, L.L.D., 96 Quantifying stimulus-evoked responses, in singleunit studies, 116-117 Quantifying transmitter-induced responses, in single-unit studies, 117 Quiet-waking, EEG/EMG scoring of, 248 R Radioimmunoassay methods, 52 Rasters, 152 See also Spike trains Rat See also Trigeminal somatosensory system, rodent as animal model, 215-216 2345_frame_IDX Page 279 Tuesday, October 29, 2002 10:58 AM Index in-dwelling subcutaneous electrode in, 217, 218 Reacquisition, of drug self-administration, 27-28 Realtime Acquisition System Programs for Unit Timing in Neuroscience (RASPUTIN), 218, 220 Rehabilitation treatment programs, lack of success of, 119 Reinforcement of drug addiction, and behavioral and drug history, 23 in cocaine self-administration, 22 cocaine vs food for, 30-31 fixed-ratio schedules for, 22, 28, 29-31 neurobiology of, 42 progressive-ratio schedules for, 31-33 second-order schedules of, 33 Reinforcers drug vs nondrug, 21 rate-increasing effect of, 25 Reinitiation, in self-administration, 18 Reinstatement, of drug self-administration, 27-28 Relapse animal models of, disorder, and reinstatement of drug self-administration, 27-28 REM (rapid eye movement) sleep EEG activation associated with, 242 EEG/EMG scoring of, 250 effects of isoproterenol on, 255, 257 and tonic discharge activity, 253 Responding in animal models, 21-22 cocaine-maintained, 20 RESPONSE analysis function, 225, 227, 229 Response latency, drug-induced changes in, 118 Response threshold, drug-induced changes in, 118-119 Responsivity to conditioned stimuli, effect of addictive drugs on, Reuptake, voltammetric study of, 97-98 Reward, drug in chronic recording studies, 195 in drug addiction, Reward-limbic networks, 214 Reward-seeking behavior in cocaine studies, 189-190 and firing patterns, 184 spike train data recorded during, 151-157 Rheodyne-style injector, 68 Ringers' perfusion fluid, 62 Rodents See Animal models; Rat 279 S Scattergram, in waveform analysis, 170, 224 Second-order schedules, in self-administration studies, 33 Self-administration of addictive compounds, 1-2 acquisition of, 28 chronic extracellular recording of, 163 (See also chronic extracellular recording) effects of repeated, 190-192 in extracellular recording studies, 162 long-term effects of, 134 maintenance of, 29 neurobiological basis of, 157 operant chambers for study of, 168 three phases of, 18 Self-administration procedures dose-response curve in, 19, 21 early research in, 19-21 methodology, 28-33 potential abuse liability and, 31 rodent, 17-18 Self-administration studies apparatus for, 33-38 in drug use determination, 22-23 subjects for, 33 Sensitization, physiological bases for, 132 Sensory-signal processing effects of cocaine on, 226 impact of psychoactive substances on, 231 monoamine influences on, 121-122 Sensory system, model, 215-216 See also trigeminal somatosensory system, rodent Serial recording methods, limitations of, 233 Serotonin (5-HT) and AMPH-induced locomotor activity and stereotypy, 247 detection of, 52, 53 detection of sub-pg amounts of, 70-71 in dialysate sample, 77 effect of cocaine on, 131 effects of methamphetamine on, 77, 79 effects of stimulant drugs on, 77, 120 METH-induced increases in, 81 in sensory neocortical circuits, 121 standard curves for, 73 voltammetric measures of, 96 Serotonin (5-HT) transporters (SERT), 77 Shock, electric, as reinforcer, 25 Silicon-based sensors, 91 Single-neuron studies in drug-related behaviors, and waveform analysis, 169, 170 Single-unit studies 2345_frame_IDX Page 280 Tuesday, October 29, 2002 10:58 AM 280 Methods in Drug Abuse Research: Cellular and Circuit Level Analyses data analysis in, 116-119 drawback of, 119 drug application in, 114-115 drug-induced changes in, 117-119 experimental protocols in, 115-116 in intact, anesthetized preparations, 112-119 recording techniques, 231 results in, 119 in spike train activity, 224-228 Skull, rat, 62 Sleep See REM sleep; slow-wave sleep Sleep-wake states behavior-based assessment of, 250-251 EEG/EMG-based assessment of, 249-250 Slow-wave sleep EEG/EMG scoring of, 250 and tonic discharge activity, 253 Software chromatographic, 72 for chronic extracellular recordings, 201-202 for many-neuron recording technique, 147148 NeuroExplorer, 148, 224 RASPUTIN, 218, 220 Solute recovery in dialysate sample, 55-56 relative vs absolute, 55-57 Spike-train activity across drug-induced states, 221 drug actions on, 231 functional connectivity in, 228-229, 232 population data for, 228-230 single-unit data in, 224-228 Spike-train analyses, 232 Spike trains ensemble analyses of, 154-157, 158 from individual neurons, 114 neuronal pairs and, 152-154 single-neuron, 151-153 Spontaneous discharge, drug-induced changes in, 117-118 Standard curves, 72-74 Statistical approaches, to firing patterns analysis, 175, 178 Stereotaxic surgery, 202-203, 248 Stimulant-dependency, treatment of, 80 Stimulant drugs acute effects of, 75-78 chronic effects of, 78-79 electrophysiological study of, 119-120 illicit, 75 in vivo microdialysis in study of, 52-53 neuroadaptive changes in brain produced by, 78 neurochemical actions of, 242-243 neurotransmission and, 75 voltammetric study of, 101-104 Stimulus-evoked responses, in single-unit studies, 116-117 Stranger software, 148 Stress, environmental, in self-administration studies, 23 Substance abuse, physiological mechanisms in, 112 Substantia innominata (SI), in sleep/wake studies, 255, 256 Substantia nigra, 100 Swivels in chronic extracellular recording, 196, 197 in self-administration studies, 35, 37 T Temporal patterns, and drug-related behavior, 20 Testing chamber See also Operant chambers for alert waking study, 252-253 in vivo microdialysis within, 60 Plexiglas, 251 Tethering system, in chronic extracellular recording studies, 198-200 Thalamic neurons, effect of cocaine on, 129-132 Thalamocortical neuron function, and LC-NE system, 226, 227, 232 Thalamus effect of cocaine on VPM, 130, 133 effects of psychostimulants on somatosensory, 125 THC (cannabinoids), voltammetric study of, 104 Time-out (TO) procedure, 29 Timing, and drug-related behavior, 20 Timolol EEG effects of, 255 effects on AMPH-induced cortical EEG activation, 263 impact on arousal of, 258, 259 Tolerance, physiological bases for, 132 Transmitter-induced responses, in single-unit studies, 117 TRIAL analysis function, 226, 227, 229 Trigeminal somatosensory system, rodent, 214, 215 equipment in study of, 217, 218 physiology of, 215-216 recording procedures with, 217-218, 219 U UniJet microbore valve, 68, 69 2345_frame_IDX Page 281 Tuesday, October 29, 2002 10:58 AM Index Uptake/reuptake, voltammetric study of, 97-98 V Ventral tegmental area (VTA), 75, 76 Videotape analysis in chronic extracellular recording, 186-187 of multineuron recording system, 224 of sleep-wake states, 251 Voltammetric recordings, 88 Voltammetry drug abuse applications of, 101-104 fast-scan cyclic, 94-95 Voltammetry, in vivo brain slices in, 98-100 electrochemical properties of chemicals in, 89 electrodes used in, 90-93 experimental paradigms studied with, 97-101 instrumentation for, 95-96 principles of, 88, 89 quantification and identification in, 95 recording methods for, 7, 93-95 scope of, 96-101 with whole animals, 100-101 VPM pathway, 215-216 281 W Waking EEG activation associated with, 242 and role of neurotransmission, 252-253 Waveform analysis, of electrophysiological data, 169-171 Waveform discrimination, in multineuron recording system, 221-224 Whisker pad, individual vibrissae on, 215, 217 Wilcoxon Matched Pairs Test, 175 Withdrawal from addictive drugs negative affective states associated with, symptoms of, Workstation, in vivo microdialysis, 67 See also Testing chamber X XcorrStat function, 226 2345_frame_IDX Page 282 Tuesday, October 29, 2002 10:58 AM ... mean interinjection interval and total drug intake Increasing doses of cocaine resulted in dose-related decreases in the number of ratios completed and increases in the mean interinjection interval... changes in the self-administration of cocaine during extended session durations has demonstrated a dysregulation in the self-administration of the drug resulting in a considerable increase in drug intake.22... presented in Figure 2.2 This figure illustrates the effects of increasing the dose of heroin on responding maintained by an FR 10 schedule of reinforcement Increasing doses of heroin from to 50 mg/inf