DOPAMINE This page intentionally left blank HANDBOOK OF CHEMICAL NEUROANATOMY Series Editors: A Bjoărklund and T Hoăkfelt Volume 21 DOPAMINE Editors: S.B DUNNETT Brain Repair Group, School of Biosciences Cardiff University, Museum Avenue Cardiff CF10 3US, UK M BENTIVOGLIO Department of Morphological and Biomedical Sciences Faculty of Medicine, Strada Le Grazie 37134 Verona, Italy A BJOăRKLUND Section for Neurobiology, Wallenberg Neuroscience Center Solvegatan 17, 223 50 Lund, Sweden T HOăKFELT Department of Neuroscience, Retzius Laboratory Karolinska Institutet, Retzius vaăg SE 17177 Stockholm, Sweden 2005 Amsterdam – Boston – Heidelberg – London – New York – Oxford Paris – San Diego – San Francisco – Singapore – Sydney – Tokyo ELSEVIER B.V Sara Burgerhartstraat 25 P.O Box 211 1000 AE Amsterdam The Netherlands ELSEVIER Inc 525 B Street Suite 1900, San Diego CA 92101-4495 USA ELSEVIER Ltd The Boulevard Langford Lane, Kidlington Oxford OX5 1GB UK ELSEVIER Ltd 84 Theobalds Road London WC1X 8RR UK ß 2005 Elsevier B.V All rights reserved This work is protected under copyright by Elsevier B.V., and the following terms and conditions apply to its use: Photocopying Single photocopies of single chapters may be made for personal use as allowed by national copyright laws Permission of the Publisher and payment of a fee is required for all other photocopying, including multiple or systematic copying, copying for advertising or promotional purposes, resale, and all forms of document delivery Special rates are available for educational institutions that wish to make photocopies for non-profit educational classroom use Permissions may be sought directly from Elsevier’s Rights Department in Oxford, UK: phone (ỵ44) 1865 843830, fax (ỵ44) 1865 853333, e-mail: permissions@elsevier.com Requests may also be completed on-line via the Elsevier homepage (http://www elsevier.com/locate/permissions) In the USA, users may clear permissions and make payments through the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, USA; phone: (ỵ1) (978) 7508400, fax: (ỵ1) (978) 7504744, and in the UK through the Copyright Licensing Agency Rapid Clearance Service (CLARCS), 90 Tottenham Court Road, London W1P 0LP, UK; phone: (ỵ44) 20 7631 5555; fax: (ỵ44) 20 7631 5500 Other countries may have a local reprographic rights agency for payments Derivative Works Tables of contents may be reproduced for internal circulation, but permission of the Publisher is required for external resale or distribution of such material Permission of the Publisher is required for all other derivative works, including compilations and translations Electronic Storage or Usage Permission of the Publisher is required to store or use electronically any material contained in this work, including any chapter or part of a chapter Except as outlined above, no part of this work may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without prior written permission of the Publisher Address permissions requests to: Elsevier’s Rights Department, at the fax and e-mail addresses noted above Notice No responsibility is assumed by the Publisher for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions or ideas contained in the material herein Because of rapid advances in the medical sciences, in particular, independent verification of diagnoses and drug dosages should be made First edition 2005 Library of Congress Cataloging in Publication Data A catalog record is available from the Library of Congress British Library Cataloguing in Publication Data A catalogue record is available from the British Library ISBN: ISBN: ISSN: 0-444-51778-2 (this volume) 0-444-90340-2 (series) 0924-8196 (series) The paper used in this publication meets the requirements of ANSI/NISO Z39.48-1992 (Permanence of Paper) Printed in The Netherlands List of Contributors G.W ARBUTHNOTT (p 199) University of Edinburgh Centre for Neuroscience Department of Preclinical Veterinary Sciences R.(D.) S.V.S Summerhall, Edinburgh EH9 1QH, UK E-mail: g.arbuthnott@ed.ac.uk S.B DUNNETT (p 237) Brain Repair Group School of Biosciences Cardiff University Museum Avenue, Box 911 Cardiff CF10 3US Wales, UK E-mail: dunnettsb@cf.ac.uk M BENTIVOGLIO (p 1) Department of Morphological and Biomedical Sciences Faculty of Medicine University of Verona Strada Le Grazie 37134 Verona, Italy E-mail: marina.bentivoglio@univr.it J.-A GIRAULT (p 109) Institut National de la Sante´ et de la Recherche Me´dicale and Universite´ Pierre et Marie Curie INSERM/UPMC U536 Institut du Fer a` Moulin 17 rue du Fer a` Moulin 75005 Paris, France E-mail: girault@infobiogen.fr A BJOăRKLUND Section for Neurobiology Wallenberg Neuroscience Center Solvegatan 17 22340 Lund, Sweden E-mail: anders.bjorklund@mphy.lu.se G DI CHIARA (p 303) Department of Toxicology and Centre of Excellence for Studies on Addiction University of Cagliari and Institute of Neuroscience Consiglio Nazionale delle Ricerche V Ospedale 72 09124 Cagliari, Italy E-mail: gadichia@tiscali.it J DRAGO (p 153) Neural Injury and Repair Group The Howard Florey Institute The University of Melbourne Royal Parade, Parkville Victoria 3052, Australia E-mail: j.drago@hfi.unimelb.edu.au P GREENGARD Rockefeller University Molecular and Cellular Neuroscience 1230 York Avenue, Box 296 New York, NY 10021, USA E-mail: greengd@rockvax.rockefeller.edu H HALL (p 525) Karolinska Institute Department of Clinical Neuroscience Psychiatry Section Karolinska Hospital S-171 76 Stockholm, Sweden E-mail: Hakan.Hall@cns.ki.se D HERVE´ (p 109) Institut National de la Sante´ et de la Recherche Me´dicale and Universite´ Pierre et Marie Curie INSERM/UPMC U536 Institut du Fer a` Moulin 17 rue du Fer a` Moulin 75005 Paris, France E-mail: herve.daniel@snv.jussieu.fr v List of Contributors T HOăKFELT Department of Neuroscience Retzius Laboratory Karolinska Institutet Retzius vaăg SE 17177 Stockholm, Sweden E-mail: tomas.hokfelt@neuro.ki.se M.K HORNE (p 153) Neural Injury and Repair Group The Howard Florey Institute The University of Melbourne Royal Parade, Parkville Victoria 3052, Australia E-mail: malcolm.horne@med.monash edu.au Y.L HURD (p 525) Karolinska Institute Department of Clinical Neuroscience Psychiatry Section Karolinska Hospital S-171 76 Stockholm, Sweden E-mail: yasmin.hurd@cns.ki.se K.J LOOKINGLAND (p 435) Department of Pharmacology and Toxicology B-432 Life Sciences Building Michigan State University East Lansing, MI 48824, USA E-mail: lookingl@pilot.msu.edu M MORELLI (p 1) Department of Toxicology and Center of Excellence for Neurobiology of Dependence University of Cagliari Cagliari, Italy E-mail: morelli@unica.it vi K.E MOORE (p 435) Department of Pharmacology and Toxicology B-432 Life Sciences Building Michigan State University East Lansing, MI 48824 USA E-mail: moorek@pilot.msu.edu J NUNAN (p 153) Neural Injury and Repair Group The Howard Florey Institute The University of Melbourne Royal Parade Parkville, Victoria 3052 Australia E-mail: j.nunan@hfi.unimelb.edu.au T.W ROBBINS (p 395) Department of Experimental Psychology University of Cambridge Downing Street Cambridge CB2 3EB UK E-mail: twr2@cus.cam.ac.uk J.R WICKENS (p 199) Department of Anatomy and Structural Biology University of Otago Medical School P.O Box 913 Dunedin New Zealand E-mail: jeff.wickens@stonebow.otago ac.nz Foreword for the Handbook of Chemical Neuroanatomy By Paul Greengard For a period of about 40 years, from 1930 until 1970, a vigorous debate raged within the neuroscience community as to the mechanisms underlying what we today call fast synaptic transmission There were two schools of thought The electrical school argued that as the nerve impulse reached the axon terminal, the wave of depolarization caused a change in the electric field across the postsynaptic plasma membrane resulting in an excitatory or an inhibitory post synaptic potential The chemical school argued that the wave of depolarization at the nerve terminal, associated with the arrival of the nerve impulse, caused an influx of calcium through voltage-sensitive calcium channels and resulted in the fusion of neurotransmitter-containing vesicles with the presynaptic membrane, the ensuing release of neurotransmitter and the activation of hypothetical receptors in the postsynaptic membrane The debate ended in a resounding victory for the chemical school It is now clear that over 99% of all fast synaptic communication between nerve cells in the brain is chemical in nature We also know that the neurotransmitter, released from the presynaptic terminal, activates the ligand-operated ion channels initiating a physiological response in the target cell The role, and even the existence, of slow synaptic transmission was even more hotly debated Some of the strongest evidence in support of the slow chemical transmission came from studies of the neurotransmitter/neuromodulator dopamine The studies by Arvid Carlsson and his colleagues, and by other investigators who followed shortly thereafter, provided compelling evidence that Parkinson’s disease was attributable to the degeneration of the dopaminergic neurons with the resultant loss of regulation by dopamine of target cells in the neostriatum The fact that levodopa treatment could abolish the symptoms of Parkinsonism, both in the experimental animals and patients, finally convinced the neuroscience community of the important role this biogenic amine plays in communication between nerve cells Studies of the mechanisms by which slow-acting neurotransmitters produce their effects on their target cells have revealed unexpectedly complex signaling pathways As a result of the complexity of the mechanisms underlying slow synaptic transmission, compared to fast synaptic transmission, the literature on slow signaling pathways has become the dominant literature in the field The vital and complex roles that dopamine and other biogenic amines play in the physiology and the pathophysiology of the brain have become subjects of increasingly intense scientific investigation The literature on dopamine alone is now so vast that it is almost impossible for any one scientist to follow it This volume of The Handbook of Chemical Neuroanatomy, coming after more than 20 years since the initial volume in this series, will be of great help for anyone trying to cope with this ever-burgeoning literature vii Preface In this, the 21st volume of the Handbook of Chemical Neuroanatomy, we are revisiting the topic of Dopamine systems of the forebrain, first covered 20 years ago in the 2nd volume in the series on Classical Neurotransmitters of the CNS In the earlier volume, the anatomy of dopamine, noradrenaline and adrenaline systems has been described in detail The chapter on the dopamine pathways of the forebrain, by Bjoărklund and Lindvall giving a detailed mapping of the ascending dopamine system, provided a classic account that remains little changed even after two decades, other than in the fine detail By contrast, what has changed dramatically in the intervening years has been the very many developments in our understanding of the functional organization of all forebrain transmitter systems, not just dopamine Our understanding of dopamine systems in particular, has been profoundly influenced by the advent of new techniques in molecular biology, neurogenetics, single cell and membrane physiology, and clinical neurology, neuropsychiatry and brain imaging in vivo In this volume, we seek to provide a systematic overview of the major recent developments in our understanding of the chemical neuroanatomy of the forebrain dopamine systems from a functional perspective Nowadays, it requires a whole volume dedicated just to dopamine in order to provide comprehensive reviews of the key developments for this one neurotransmitter After a generous foreword by Paul Greengard, in the first chapter, Bentivoglio and Morelli provide a systematic overview of the morphological and neurochemical background on the organisation of the midbrain dopamine systems and their ascending forebrain projections and receptors, to provide the anatomical foundation and overall context for the more specific themes in each of the subsequent chapters Horne et al then consider the opportunities of transgenic technologies to understand the roles of different classes of dopamine receptors both in mediating functional processes, such as reward and in regulating neuronal plasticity and sprouting The molecular focus on receptors is then carried forward by Herve´ and Girault, in reviewing the alternative mechanisms of signal transduction by G proteins and cAMP at the different classes of dopamine receptors The physiological consequences of such interactions are then considered by Wickens and Arbuthnott, discussing the functional implications of the spatial and temporal specificity of the dopamine signal The dopamine system has been one of the major foci of attention in the behavioral neurosciences throughout this period, because of the pharmacological and the toxic tools available for its selective manipulation and the resulting dramatic influences on key dimensions of motor, motivational and cognitive functions Consequently the following three chapters by Dunnett, Di Chiara, and Robbins in turn review the recent developments in each of these domains of behavioral function Next, the chapter by Lookingland and Moore provides a separate consideration to the hypothalamic dopamine systems and the very different endocrine functions also subserved by dopamine neurotransmission Finally, Hurd and Hall consider the uniquely human disturbances in psychiatric function, associated with changes in dopamine transmission, from the perspective provided by recent developments in imaging, both in vivo and postmortem ix Preface The editors wish to thank all the authors who have responded so willingly to contribute their time and expertise in preparing their individual chapters to a consistently high standard We hope that you find the resulting synthesis a welcome addition to the literature by providing systematic critical reviews and a lasting reference source of contemporary developments in the functional neuroanatomy of the forebrain dopamine systems STEPHEN DUNNETT (Cardiff, Wales, UK) MARINA BENTIVOGLIO (Verona, Italy) ANDERS BJOăRKLUND (Lund, Sweden) TOMAS HOăKFELT (Stockholm, Sweden) x May 2004 Index Bradykinesia, 43, 162, 237, 266–269, 278, 417 Brain size, 158 Bromocriptine, 325, 341, 419–422, 468–471 Burst firing (see also Electrophysiology), 26, 35, 209–215, 249, 319, 340, 348, 399 Cajal, Ramon Santiago y, 11–13, 17, 24 Calbindin, 10, 22, 23, 31–33, 53, 71, 74, 167, 356, 527, 531, 533 Calcineurin, 112–119, 126, 221 Calcium channels, vii, 74, 115, 118, 120, 126, 130–132, 136, 155, 161, 217–223 Calcyon, 121, 122, 555 Calmodulin, 114, 116, 122, 134 Calretinin, 31, 32, 305 cAMP responsive element binding protein (CREB), 121, 123, 133–136 cAMP-dependent protein kinase (PKA), 112–125, 134 cAMP-regulated phosphoprotein, 117, 118 Cannabinoids, 109, 354 CANTAB neurological test battery, 417–422 Carbidopa, 238 Carli task, 264–266 Carlsson, Arvid, vii, 5, 110, 237, 238, 239, 243 Casein kinase (CK), 116 Castration (orchidectomy), 470–472, 483, 493 Cat, 5, 9, 13, 16, 20, 43, 45, 50, 210, 350, 531, 547 Catalepsy, 160, 162, 238–240, 244, 246, 251, 277 Cataplexy, 162–165 Catecholamine (see also individual transmitters), 5–9, 20, 49, 60, 61, 237, 238, 245–248, 252, 269, 347, 444–448, 468 Catecholamine fluorescence, 5, 238, 441–445, 468 Catechol-O-methyltransferase (COMT), 424, 425, 446 Caudate nucleus (see also neostriatum), 8, 26, 38, 39, 45–48, 53, 54, 62, 65, 69, 73, 74, 78–82, 109, 124, 154, 238, 240, 266, 267, 343, 348, 354, 355, 401–403, 407, 408, 412, 417, 530–532, 536–544, 547, 550, 551, 556 Caudate-putamen (see also neostriatum), 26, 45, 48, 53, 54, 62, 69, 82, 240, 343, 354, 355, 401–403, 551 Cell counts, 21, 209, 271, 275 Cell cycle, 159, 179 Cell morphology, 23, 202, 438, 541 Cell size, 52, 77, 209, 439, 440, 445, 446 Central executive system, 410 Central grey, 306, 528 Cerebellar grafts, 273 Cerebellum, 4, 10, 14, 44, 68, 74, 78, 80, 84, 86, 166, 272, 273, 535–538, 544, 548–551 Cerebral blood flow, 416–421 Cerebral peduncle, 3, 10–14, 17, 22, 36 CGP3466B, 270 Chemokines, 37 Chewing, 157, 168 Chlorpromazine, 239, 263, 326, 329 CHO cells, 127–132, 215 Choice reaction time, 261–266, 406 Cholecystokinin (CCK), 32, 33, 49 Choroid plexus, 466, 492, 493 Cingulate cortex, 29, 56, 62, 63, 68–77, 83, 154, 155, 533, 534, 550, 555 Circadian rhythms, 59, 158, 435, 436, 464, 477, 479, 486–491, 495 Circling rat, 274 Citalopram, 342 cJun, 133–135, 160, 449 cJun N-terminal kinase (JNK), 123, 127 Claustrum, 38, 68, 78, 537, 538, 545 Cloned receptors, 110 Clozapine, 84, 168–170, 419, 452, 558 Cobalt, 272 Cocaine, 31, 56, 57, 112, 113, 116, 123, 133–135, 154–160, 163, 169–173, 183, 210, 257, 276, 277, 321–326, 330–332, 338–344, 352–368, 395, 548–554 Cognition, ix, 1, 2, 29, 63, 71, 73, 83, 84, 88, 154, 157, 168, 251, 268, 304, 363, 364, 395–426, 525, 535, 548, 551, 554, 555, 558 Collateral sprouting, 250 Colloidal gold, 23 Co-localisation, 213–215 Compensation, 174, 181–184, 247–252, 274, 276 Computational models, 395–397, 423, 426 Conditioned (secondary) reinforcement, 322–328, 366, 373 Conditioned fear, 170, 277, 401 Conditioned place preference, 123, 134, 135, 160–164, 183, 325–334, 340, 342, 366 Conditioned response, 258, 259, 308 Conditioned rotation, 258, 259 Conditioned stimuli, 303–309, 316, 320–328, 333–337, 351–353, 361–371, 397–404 Conditioned suppression, 401–404 Conditioned taste aversion, 333–335, 351 575 Index Connexin, 25 Continuous reinforcement (CRF) schedule, 262, 309, 321, 338 Conveyor belt, 261 Copulation, 320, 366, 472 Cortical lesions, 3, 406–409, 415 Corticocortical projections, 42, 71, 77 Corticosterone, 463 Corticostriatal projections, 39–49, 54, 71, 77, 120, 199–205, 216–227, 532, 534 Corticothalamic projections, 71 Corticotropin releasing hormone (CRH), 463–465, 474, 479, 495, 496 Cow, 110 Craving, 364–368 Cresyl violet, 27, 271 Crossed projections, 49, 250 CY 208–243, 451 Cyclic AMP (cAMP), ix, 79, 110–136, 155, 161–170, 179, 204, 214, 215, 221, 412, 449, 454, 474 Cyclin-dependent kinase (CDK), 116 Cylinder test, 260 Cytoarchitecture, 1, 447 Cytochrome oxidase (COX), 163 D-Ala(2)-MePhe(4)-Gly(5)-ol] enkephalin (DAMGO), 337 Deafness, 274 Deep brain stimulation, 43 Dehydration, 245, 456 Delayed alternation test, 271, 410, 414 Delayed response test, 135, 410–416, 424 Delirium, 552, 554 Deltorphin, 483 Delusions, 395, 554 Dendrites, 11–24, 29–33, 40, 50–59, 63, 68, 73–77, 85, 88, 183, 200, 204–207, 214, 221–225, 439–443, 449, 451, 481, 485, 489, 534, 545–547 Dendritic spines, 40, 48–55, 63, 64, 68, 73–77, 84–88, 117, 182, 183, 200–207, 225, 226, 529, 534, 540, 545, 546 Dendrodendritic synapses, 1, 24, 25 Dentate gyrus, 10–14, 62, 65, 69, 72, 73, 78, 82–86, 177, 534, 537, 542–547 Dependence, 89, 118, 220, 251, 253, 309, 310, 344, 362–365 Deprenyl, 270 Depression (see also Affective disorder), 318, 363, 425, 556, 557 576 Development, 2, 3, 9, 37, 43, 60, 118, 133, 155–158, 166, 173–177, 238–252, 256, 265–268, 273–278, 435–439, 443–445, 451, 459–468, 525–529, 535–543, 552, 558 Diagnostic Statistical Manual (DSM), 364, 365 Diagonal band of Broca, 58, 59, 80, 437, 441, 458, 496, 540 Diazepam, 421 Differential reinforcement, 262 Digging, 244 Dihydrotestosterone, 439, 471 Dihydroxyphenylacetic acid (DOPAC), 169, 173, 249, 258, 270–274, 346–350, 360, 414, 445–449, 456, 476, 494 Dihydroxyphenylalanine (DOPA), 238, 252, 257, 266, 276, 439, 443–448, 490, 494, 556 Direct pathway, 33, 39, 43, 51, 68, 156, 163 Directed behaviour, 244, 336, 415 Discrete trial tasks, 263 Discriminative stimuli, 170, 171, 306, 320–325, 337, 353, 403, 407, 408 Distractibility, 407, 408, 423 Dog, 35, 491 Domperidone, 166, 216 DOPAC/DA ratio, 350, 414, 448, 449 Dopa-decarboxylase (DDC, see also AADC), 257, 439–448, 490 DOPAergic neurons, 440, 441, 460, 466, 474, 486, 489 Dopamine, 1–559 Release, 25, 26, 30–33, 38, 44, 50, 77, 123, 125, 164–169, 175, 179–182, 200–203, 209–213, 223–226, 249, 250, 256–258, 274, 276, 303, 319, 325, 331, 347–355, 362, 366, 369, 395, 400, 418–423, 438–449, 45–455, 460, 463, 466, 472–479, 489, 490, 494, 495, 525, 547, 548, 556 Storage, 25, 31, 173, 174, 276 Synthesis, 7, 165, 173, 175, 179, 248–252, 257, 258, 275, 277, 322, 438, 440, 445, 448, 454–459, 466, 478, 490, 525–527, 540 Terminals, 68, 71, 173–183, 202–204, 209, 211, 240, 249, 267, 271, 278, 323, 332, 342, 356, 441, 445, 452, 529, 534, 547, 548, 553 Transmission, ix, 25, 56, 71, 109, 132–137, 204, 238, 277, 303, 304, 310–334, 338, 342–357, 360–362, 365–373, 399, 416 Turnover, 168, 169, 259–263, 273–278, 400, 414, 478, 492 Uptake, 31, 34, 51, 165, 178, 207, 211, 212, 226, 249, 257, 276, 325, 354–358, 447, 464, 525, 547 Index Dopamine and cAMP-regulated phosphoprotein (DARPP-32), 112–128, 165 Dopamine receptors, ix, 1, 2, 28, 39, 41, 44, 50, 51, 66–88, 109–137, 153–183, 199, 204–207, 211–227, 239–243, 249, 252, 259, 276–278, 303, 311–315, 320–335, 339–345, 395, 397, 404–406, 412, 414, 421, 423, 436, 442, 446, 450–452, 456–465, 477, 478, 488, 490, 494, 496, 525, 535, 536, 539–548, 552–558 D1 receptor, 1, 39, 51, 66–82, 86–88, 111–123, 126–128, 133–136, 154–160, 167–171, 183, 204–207, 213–227, 239, 240, 252, 253, 257, 259, 263, 277, 315–325, 329–339, 343–345, 357, 397, 401–406, 411–415, 421–425, 446, 450–464, 472, 478, 494, 535–541, 545, 546–558 D2 receptor, 1, 39, 51, 6–84, 111, 115, 124–136, 154, 155, 160–169, 173–183, 202–207, 213–227, 239, 240, 249, 252, 257, 259, 263, 273, 277, 278, 315, 317, 321–325, 329, 330, 334, 335, 339–348, 401–406, 411, 412, 419–425, 440, 446–464, 472, 478, 487, 494, 495, 528, 535–558 D3 receptor, 1, 66, 67, 71, 79–84, 111, 125–132, 154, 166, 219, 277, 278, 401–405, 451, 535, 537–546, 554–558 D4 receptor, 1, 66, 67, 79, 83–86, 111, 131, 132, 154, 168, 169, 222, 277, 278, 405, 425, 451, 456, 535, 544–546, 554–558 D5 receptor, 66, 67, 73, 86–88, 111, 113, 120–122, 154, 170, 204, 239, 277, 397, 451, 535, 538, 545, 546, 558 Dopamine transporter (DAT), 22, 29–31, 44, 51, 55, 56, 60–65, 159, 165, 172–182, 207–211, 226, 274–277, 314, 332, 342–344, 355, 409, 440, 447, 453, 494, 528, 529, 539, 546–553, 557 Dopaminergic phenotype, 1, 7, 177, 275, 276 Dopamine-b-hydroxylase (DBH), 239, 276, 445, 448 Dorsal noradrenergic bundle, 246 Dorsal striatal lesions, 265 Dorsal striatum, 45, 53–56, 79, 83, 86, 154, 156, 172–178, 212, 225, 240, 254, 257, 266, 274, 305, 335, 342, 343, 354–358, 365, 367, 396, 397, 402, 403, 414, 530, 531, 536, 543–546, 553, 557 Dose-response, 242, 243, 338–340, 422 d-Pen(2),d-Pen(5) enkephalin (DPDPE), 483, 485 Drinking (see also Thirst), 157, 244, 250, 251, 271, 313, 329, 341, 342 Drive, 183, 245, 313, 321 Drug abuse, 30, 31, 53, 56, 89, 109, 113, 160, 163, 226, 242, 322, 324, 331, 338, 341, 344, 354–357, 363, 366, 371, 373, 395, 548–550 Drug-induced dyskinesia, 182 Drug-seeking behaviour, 363, 364 Dwarf mice, 467, 468 Dynorphin, 33, 68, 76, 133–136, 156–163, 167, 168, 480–483, 489, 492, 495 Dyskinesia, 182, 238, 250, 266, 555 Dysphoria, 345, 551 Eating (see also Hunger), 112, 157, 244–247, 251, 260, 267, 276, 305–309, 313, 315, 323, 337, 348–350, 369–372, 401, 493 Ecstasy, 354 Edinger, Ludwig, 3, Edinger-Westphal nucleus, 12, 14, 19 Ejaculation, 320, 472 Electrical stimulation, 43, 212, 223, 257, 329, 353, 361, 487 Electrochemical recording (Voltammetry), 165, 207, 212, 276, 310, 342, 346, 347, 353, 360, 361, 398 Electrolytic lesions, 61, 243, 254, 323 Electron microscopy, 7, 13, 24, 25, 29, 31, 50, 55, 63–68, 73, 76, 85, 87, 179, 200, 204, 214, 486, 529, 540, 545–547 Electrophysiology, 2, 25, 26, 29, 30, 34, 35, 53, 67, 77, 80, 110, 119, 120, 156, 157, 160, 165, 173, 199, 202, 209–227, 249, 250, 273, 279, 310, 342–355, 360, 395–400, 423, 451, 468, 479, 486, 540 Elevated body swing test, 259 Elevated plus maze, 167, 169, 277, 278 Embryonic death, 275, 276 Embryonic/fetal development, 124, 155–158, 272–276, 438, 466, 526, 527, 535, 541–546 Emonapride, 544 Emotion, 355, 535 Endoplasmic reticulum, 25, 73 Engrailed gene, 275 Enkephalin, 33, 51, 76–80, 134–136, 156–163, 167, 168, 214, 220, 473, 480–485, 492, 495 Entopeduncular nucleus (see also Globus pallidus), 38, 62, 155, 163 Entorhinal cortex, 61–64, 68–74, 78, 84, 86, 154, 530–534, 545, 547, 556 577 Index Entrainment, 488 Environment, 28, 158, 169, 210–215, 259, 272, 278, 308–312, 322, 328, 366, 398, 414, 415, 425, 471, 550, 557 Epidepride, 539, 542, 557 Epilepsy, 274 Estradiol, 439, 459, 487, 490 Estrogen, 442, 453, 459, 466–471, 476–489, 495 Estrus, 320, 459, 488 Ethanol (see also Alcohol), 160, 164, 169, 170, 277, 322, 330, 341, 342, 354–356, 369 Ether, 493 Ethological evaluation, 157 Eticlopride, 127, 133 Euphoria, 303, 318, 344, 345, 350, 354, 368, 372, 549 Evans Blue, 23 Excitotoxic lesions, 245, 311, 397, 406, 411 Executive function, 304, 336, 410–412, 417–426 Exocytosis, 25, 446, 548 Exploration, 121, 157, 169, 244, 245, 273–278 Extended amygdala, 1, 29, 53, 57–59, 303–306, 355, 533 Extinction, 56, 309–316, 321, 325, 328, 332, 339, 340, 353, 361, 399 Extracellular signal-related kinase (ERK), 116, 123, 127–134 Extra-dimensional shift, 406–409, 416–420 Extrapyramidal system, 38 Facial expression, 266 F-actin, 117 Familial Parkinson’s disease, 278, 279 Fasciculus retroflexus, 6, 9–16, 36, 57 Fast Blue, 23 Fear, 170, 245, 277, 278, 401 Fenfluramine, 421 Fibres of passage, 5, 11, 245, 311 Fibroblast growth factor (FGF), 275 Finger tapping test, 421 Flexor muscles, 262 Fluorescent tracers, 49 Fluorodopa binding, 266, 556 Fluoxetine, 342, 343, 409 Flupenthixol, 263, 327, 329, 402, 404 Fluphenazine, 239, 325, 341 Flurogold, 271 Follicle-stimulating hormone, 479 Food reward, 263–269, 306, 314, 344, 352, 361, 370, 396, 413 Footprint test, 259 578 Forel, August, 40, 46 Forepaw placing, 260 Fornix, 10, 62, 437 Forskolin, 126–130, 134 Fos, 59, 112, 130–136, 159, 160, 440, 449–454, 459–464, 476, 482, 489, 491 Free operant tasks, 263 Free radicals, 246, 271 Frontal cortex, 30, 32, 40, 55, 61, 62, 69, 71, 77, 84, 86, 168, 267, 271–274, 395, 410, 417, 424, 530–537, 552 G protein-regulated inward rectifer Kỵ channels (GIRK), 125, 130 GABA receptor, 115, 119–122, 167, 319, 337, 480, 481, 485–489, 494, 495 Gain of function, 273 Gait, 162, 166, 259, 266, 270, 273, 274 Ganglionic eminence, 159, 179 Ganglioside GM1, 273 Gap junction, 1, 25, 26 Gastric acid secretion, 477 Gastrin-releasing peptide (GRP), 473, 477–479, 495 Gastrin-releasing peptide receptor, 473, 478 Gastrointestinal motility, 477 Genetic background, 158, 163, 164 Genetic polymorphism, 424, 425 Genetic recombination, 128 Genotype, 158, 160, 424, 425, 439, 558 Glia, 1, 25, 26, 37, 174, 176, 250, 257, 269, 443–447, 475 Glial cell line-derived neurotrophic factor (GDNF), 273 Gliosis, 273, 278 Globus pallidus, 3, 5, 26, 29, 38–43, 52–58, 69, 76, 155, 156, 163, 257, 306, 319, 531, 533, 538–547, 555 Globus pallidus lesions, 257 Glucocorticoids, 463, 464 Glucose balance, 248, 477 Glutamate, 26–30, 35, 73, 115–122, 133, 160, 199, 205, 216, 222–224, 306, 311, 326, 336, 405, 425, 441, 473, 480 Glutamate receptor, 26–30, 115–120, 133, 199, 480 Glutamic acid decarboxylase (GAD), 163 Glyoprivation, 245 Gnawing, 242, 244 Go/No go tasks, 419 Golgi apparatus, 73 Index Golgi method, 11, 13 Gonadotropin, 438, 443, 458, 473, 479, 496 Gonadotropin releasing hormone (GnRH), 458, 459, 477, 479, 496 G-protein coupled receptor, 204, 215 G-proteins, 154, 161–164, 204, 474, 480, 535 Grasp reflex, 157 Grooming, 157, 159, 168, 242, 246, 277 Growth cones, 171–177, 182, 250 Growth hormone, 157, 452, 459–461, 465–468, 473, 477, 478, 495 Growth hormone releasing hormone (GHRH), 459–461, 478 Guidance molecules, 177 Gustatory cortex, 305, 306 Gustatory receptor, 314 Habenula, 29, 55–59, 74, 80, 159 Habits, 56, 237, 263, 265, 279, 309, 310, 335, 363, 364 Habituation, 157, 158, 168, 276, 335, 349, 369–373, 398, 399 Hallucinations, 395, 417, 554 Haloperidol, 134, 136, 160, 164, 165, 173–177, 182, 183, 239–242, 252, 258, 263, 272, 313–316, 320, 325–331, 339, 341, 402, 404, 411, 412, 451, 452, 478, 558 Hamster, 155, 329, 490, 491 Head turning, 257 Hedonic properties, 277, 309–318, 322, 329, 334–337, 344, 345, 349, 350, 363, 369 Heroin, 266, 316, 320, 325, 336, 340, 342, 356–361, 550 Hippocampus, 12, 46, 48, 53, 54, 58–68, 72–88, 118–121, 170, 177, 225, 226, 237, 248, 272, 274, 278, 335, 336, 397, 402, 403, 412, 480, 530–548, 556 Histamine, 34, 464, 494 Homeostasis, 245, 251 Homovanillic acid (HVA), 267–274, 446, 447 Hormone secretion, 435, 436, 443, 452–462, 473–481, 487, 488, 495, 496 Hornykiewicz, Oleh, 5, 154, 238 Horseradish peroxidase (HRP), 5–8, 14, 16, 23, 49 Human, ix, 1–4, 11, 13, 17–21, 25, 32, 35, 43, 45, 65, 67, 73, 78–83, 86, 88, 109, 123, 131, 132, 160, 166, 170, 210, 211, 237–242, 248–254, 263–279, 307, 318, 337, 345, 354, 355, 366, 367, 395, 403–410, 416–421, 424, 425, 484, 491, 525–558 Hunched posture, 243 Hunger, 244, 245 Huntington’s disease, 109, 153, 421 Hydrogen peroxide, 246 Hyperactivity (hyperkinesia), 51, 158, 163–167, 240–243, 274–278, 322, 323, 330, 368, 409, 419, 556 Hyperdirect pathway, 1, 39–43 Hyperprolactinemia, 444, 458–471, 492–495 Hypertension, 171, 277 Hypoactivity (hypokinesia), 239, 244, 245, 267–270, 323 Hypocretin/Orexin, 33–36 Hypophysial portal vasculature, 440, 444–448, 452, 453, 459–470, 474, 475, 481, 486, 490–494 Hypoprolactinemia, 466–470 Hypothalamic lesions, 243–247, 260, 261, 267, 459, 479, 488 Hypothalamic-pituitary-adrenal axis, 464, 465, 479, 493 Hypothalamus, ix, 2, 12, 29–35, 44, 53–59, 68, 74, 80, 84, 86, 154–156, 162, 237, 243–248, 260, 261, 267, 271, 306, 329, 335, 435–496, 527, 528, 536–547 Anterior area, 34, 74, 437–443, 451, 460, 462 Arcuate nucleus, 436–449, 456, 460, 461, 466–470, 474–492 Dorsomedial nucleus, 437, 441, 476, 482–485, 528 Lateral area, 40, 53, 243–248, 306, 329, 335, 438, 443, 464 Mediobasal area, 436–441, 446, 458, 466–471, 475, 478, 481, 493 Paraventricular nucleus, 80, 437, 441, 442, 455, 457, 461–465, 474–484, 493–496, 541 Periventricular nucleus, 60, 435–443, 451–466, 474–485, 489, 495, 496, 528 Posterior area, 12, 34, 82, 253, 437 Preoptic area, 53, 437, 443, 451, 45–462, 472, 477, 481–485, 492, 496, 543 Retrochiasmatic area, 437, 441–443, 456–461 Suprachiasmatic nucleus, 68, 442, 477–484, 488, 489 Supraoptic nucleus, 69, 84, 437, 443, 455–457, 477–482, 493 Ventromedial nucleus, 80, 437, 456, 472, 484, 493, 541 Hypothermia, 467 Hypoxanthine-guanine phosphoribosyl transferase (HPRT), 252, 253 579 Index Ibotenic acid, 70 Idiopathic disease, 266, 267 Idobenzamide, 556 Immediate early genes (see also individual genes), 2, 59, 130, 133, 156, 159, 162, 449–451 Immobilisation, 262 Immune surveillance, 26 Immunogold staining, 31 Immunohistochemistry, 7–10, 17–23, 30, 31, 35, 37, 44, 50, 52, 57, 60, 66, 67, 76, 86, 157, 163, 171–177, 204, 206, 238, 356, 438–445, 449, 466–468, 474–489, 525, 526, 531, 545 Immunoprecipitation, 167 Immunotoxic lesions, 51 In situ hybridisation, 9, 25, 27, 67, 76–82, 86, 111, 156, 157, 167, 175, 214, 449, 464, 476, 492, 525–528, 535–547, 552, 554 Incentives, 56, 199, 216, 227, 303–332, 336, 337, 344, 345, 350–354, 361–373 Incertohypothalamic dopamine neurons, 437– 451, 455–458, 465–470, 476–487, 492–496 Indirect pathway, 33, 39–43, 51, 52, 88, 156 Inferior colliculus, 13 Inferior olive, 26 Inflammation, 28, 270, 464 Information processing, 1, 39–43, 57–59, 88, 396 Infundibulum, 437–442, 453, 454, 484, 487 Instrumental learning, 309, 311, 336 Insula, 54, 69, 533–538, 545 Intention tremor, 273 Internal capsule, 38, 39, 45, 46, 62, 240, 437 Interpeduncular nucleus, 10–16 Intracarotid injection, 269 Intracellular recording, 25, 216, 217, 224, 225, 486 Intracerebral administration, 239, 246, 257, 268, 311, 315, 323–326, 331–337, 341–343, 351, 356, 366, 401–408, 412–414, 420, 449 Intracranial self-stimulation (ICSS), 212, 225, 304, 311, 317, 320, 338 Intra-dimensional shift, 407, 408, 417, 420 Intraventricular lesions, 246–250, 469 Inverse-U relationship, 241, 242, 338–343, 414, 418, 422 Irritability, 246 Islands of Calleja, 54, 69, 74–83, 159, 162, 166, 538, 542, 543 Isoguvacine, 486, 487 580 JunB, 133 Kainate recaptor, 480 Kennard effect, 251 Khat, 354 Kidney, 120, 121, 157, 455, 467 Knife cut lesions, 245, 254 Knockout mice, 77, 112, 113, 121, 135, 153–184, 222, 275–278, 313, 314, 330, 339–343, 409, 424, 468 Lactation, 213, 272, 453–457, 463, 467–470, 476, 482–494 Lactotroph, 125–127, 440, 452, 453, 460, 463, 466, 473–477, 488–495 Large aspiny neurons, 45, 68, 87 Latent inhibition, 399, 403–405 Lateral hypothalamic syndrome, 243–247 Lateralisation, 268, 274 L-Dihydroxyphenylalanine (L-DOPA), 109, 110, 133, 134, 183, 238, 250, 252, 257, 263, 266, 269–277, 526 Learning, 56, 73, 110, 133, 137, 154, 157, 199, 210–216, 222–225, 251, 271, 279, 303, 307–312, 316–318, 326–336, 348–353, 363–372, 395–406, 416–422 Lenticular fasciculus, 41, 533 Lesch-Nyhan syndrome, 252 Lesion size, 172, 180–182, 264 Leucine zipper, 134 Lever pressing, 164, 251, 261, 262, 269, 311, 317, 336, 337, 352, 353, 397 Lewy body, 278 Licking, 243, 313, 314 Lidocaine, 311, 335 Lignocaine, 262 Limb clasping, 273 Limbic system, 1, 22, 40, 46, 49, 52–57, 61, 71, 77–84, 88, 109, 130, 154, 156, 162, 170, 240, 253, 304, 356, 403, 441, 481, 529–534, 538, 543, 549, 550, 555, 558 Lipopolysaccharide, 28 Lithium, 331, 334, 351 Lmx1b strain, 275 Local anaesthetic, 262, 330, 332 Locomotor activity, 68, 112, 113, 123, 135, 157–170, 239–243, 251, 252, 256–258, 268–279, 315, 322, 323, 331, 332, 340, 397, 399, 409 Index Locus coeruleus, 30, 44, 55, 61, 74, 267, 270, 306, 479 Locus coeruleus lesions, 61 Long-term depression (LTD), 110, 120, 121, 223–226, 398 Long-term memory, 335, 402 Long-term potentiation (LTP), 110, 120, 121, 183, 223, 224, 274, 397, 398, 403 Lordosis, 329 Luteinizing hormone, 443, 458, 459, 477–480, 487, 490, 495, 496 Luys, Georges Bernard, 40 LY-171555, 252 Lyon-Robbins hypothesis, 242 Magnetic Resonance Imaging (MRI), 416–419, 423, 424 Major histocompatibility complex (MHC), 37 Mamillothalamic tract, 437 Mammillary body, 74, 79, 534, 543 Manganese, 272 Mania, 318 Marchi technique, Marchi, Vittorio, Marmoset, 240, 268, 406–411 Mating, 488, 491 Matrix, 32, 39, 45–47, 50, 53, 79, 83–86, 135, 335, 531–547 Maze tests, 167–170, 315–321, 325, 335, 336, 402, 403, 410–413 Mazindol, 178, 547, 553 Mechanisms of toxicity, 267–270 Medial forebrain bundle, 16, 46, 62, 175–177, 238, 240, 245, 246, 319 Median eminence, 436–454, 458–470, 474–494 Medium spiny neurons, 45–59, 118, 119, 123–128, 220, 529, 546 Medulla oblongata, 20, 443 Melanin, 527 Melanotroph, 125, 442, 452–454, 479, 487, 494, 495 Memory, 40, 63, 65, 73, 154–158, 222, 273, 303, 306, 335, 336, 396, 397, 402–405, 409–424 Consolidation, 303, 335, 371, 373, 402, 403 Retrieval, 158, 401, 405, 413, 414, 420 Meperidine, 266 Mesocorticolimbic projections, 21, 33, 48, 52–56, 61, 63, 77, 83, 154, 163, 238, 240, 253, 304, 306, 340, 356, 365, 368, 395, 396, 399–406, 411, 415, 425, 435, 472, 476, 492, 493, 527, 535, 547–551, 558 Methadone, 363 Methamphetamine (see also Amphetamine), 169, 257, 270, 271, 354, 550–553, 558 Methylphenidate, 257, 344, 409, 419, 420, 424, 548–551 Methyl-phenylpyridinium ion (MPPỵ), 254, 269, 270 Metoclopramide, 329 Meynert, Theodor, 3, 4, 38, 540 Microdialysis, 164, 167, 210, 212, 249, 274, 276, 346–361, 367, 369, 398–400, 404, 407, 446, 472 Microglia, 26, 28, 174 Midazolam, 170 Midbrain tegmentum, 3–15, 21, 26–30, 33, 35, 40, 46–49, 56 Mingazzini, G., 3, 11 Mitochondria, 181, 202 Mitogen-activated protein kinase (MAPK), 79, 123 Mitogenesis, 79, 123, 162 MK-801, 473 Monakow, Constantin von, Monoamine oxidase (MAO), 169, 239, 246, 254, 269, 270, 446, 447, 456 Monoamine oxidase inhibitor, 246 Morphine, 113, 163, 164, 324, 325, 330–334, 340, 353, 356, 362, 369–372, 481, 482 Motivation, ix, 2, 41, 44, 56, 60, 88, 154, 157, 163, 164, 199, 200, 213, 243–248, 263, 264, 279, 303–373, 399–402, 406, 419, 422, 472, 525, 535, 548 Motor control, 5, 237–279, 525 Motor coordination, 273, 277, 279 Motor cortex, 43, 46, 52, 69, 78, 306, 529 Motor deficits, 237–279 Mouse, 2, 3, 9–26, 31–40, 45, 49, 51, 65, 80, 84, 112–114, 119, 120, 124–128, 134, 135, 153–184, 221, 222, 241, 242, 251–254, 266–279, 313, 314, 330, 339–343, 405, 409, 435, 436, 442, 444, 467, 468, 491 Mouse strains, 49, 278, 405 Movement disorder, 38, 42, 88, 153, 268, 273, 274 Muscarinic acetylcholine receptor, 29, 30, 161, 414 Muscimol, 337, 486 Naloxone, 163, 331, 491, 492 Naltrindole, 485 Nausea, 238 581 Index Nauta technique, Neglect, 245–248, 260, 265, 268, 269, 403 Neocortex (see also main cortical areas), 1, 3, 11, 20–22, 29–34, 39–64, 68–79, 83–88, 109, 110, 112, 118–121, 154, 162, 163, 183, 200, 203, 218, 219, 223–226, 237, 240, 271, 278, 303–306, 324, 336, 339, 343, 349, 350, 353, 356, 357, 362, 369, 395–425, 463, 464, 529–557 Neonatal lesions, 246, 251, 252, 273 Neostriatal mosaic (see also Striosome, Matrix), 32, 59 Neostriatum (see also Caudate, Putamen), vii, 22, 32, 38, 42, 45, 52, 201, 222–225, 237– 240, 253, 258, 262–266, 271, 272, 333 Nest building, 244 Neurabin, 117, 127 Neural tube deficits, 275 Neuroblastoma cell lines, 123, 136 Neurodegeneration, vii, 3, 5, 28, 31, 32, 57, 70, 88, 109, 175, 227, 250, 254, 266–279, 311 Neurogenesis, 65, 175, 177, 272 Neuroimaging, ix, 2, 240, 266, 268, 344, 345, 347, 364, 395, 406, 416–421, 525, 526, 548–558 Neuroleptics, 77, 84, 89, 109, 110, 132–137, 153, 168, 170, 183, 227, 239, 240, 252, 263, 303, 304, 311–330, 338–345, 401, 404, 419, 420, 452, 554–558 Neurological test battery, 260, 261 Neuromedin, 477, 478 Neuromodulator, vii, 460 Neuropeptide Y, 485, 493 Neurophysin, 456 Neuroprotection, 254, 270, 273 Neurotensin, 33, 61, 77, 80, 135, 166, 452, 473–477, 495 Neurotensin receptor, 33, 452, 474–476 NGD-94–1, 545 Nicotine, 29, 35, 109, 322, 330, 332, 340–344, 354–356, 362, 489, 557 Nicotinic acetylcholine receptor, 29, 489 Nigral grafts, 258, 264, 274 Nigrostriatal lesions (see also 6-OHDA, MPTP), 3, 56, 70, 77, 133–135, 156, 159, 171–183, 225, 226, 237, 242–274, 313, 314, 330, 410, 412 Nigrostriatal projections, 3–8, 21–24, 28, 30, 39–41, 46–54, 61, 70, 77, 83, 153–156, 167, 171, 172, 179, 182, 222, 237–278, 395, 403, 406, 410, 415, 419, 435, 467- 472, 485, 492, 527, 535, 540 582 Nigrotectal projections, 42 Nigrothalamic projections, 41, 42, 60, 534 Nissl stain, 7, 11–13, 20, 38 Nitric oxide (NO), 35, 59, 116, 270, 474, 489 Nitric oxide synthase (NOS), 35, 270 NMDA (N-methyl-d-aspartate), 35, 115–122, 134, 183, 221–225, 336, 473, 480, 495 NMDA receptor, 115–122, 134, 183, 221–225, 336, 473, 480, 495 Nomifensine, 257, 343 Noradrenaline (norepinephrine), ix, 7, 20, 30–35, 44, 55, 61, 130, 237–252, 267, 269, 276, 306, 342, 347, 354, 356, 406–410, 419, 424, 425, 443–450, 459–465, 526, 553 Noradrenaline transporter, 342, 553 Norbinaltorphimine, 483 Novelty, 157, 158, 169, 259, 271–278, 303, 322, 348–352, 493 Nucleus accumbens, 24–26, 29, 33, 41, 45–48, 52–86, 109, 113, 134, 135, 154, 155, 159–170, 212, 225, 240, 242, 257, 264–267, 272, 274, 303–306, 311–315, 321–326, 330–373, 396–406, 410–414, 530–532, 536–548, 554 Core, 24, 25, 53–56, 69, 71, 77, 80, 303–306, 311, 322–326, 331–337, 343, 347–362, 369–372, 397–400, 405, 479, 530–532, 543–546 Shell, 53–56, 64, 69, 71, 77, 80, 85, 166, 303–306, 311, 322–326, 330–337, 343, 347–362, 366–373, 398–401, 405, 530–532, 543–546, 554 Nucleus accumbens lesions, 257, 264, 321–324, 330, 332, 336, 339–342, 397, 401, 406, 410 Nucleus basalis magnocellularis (nucleus basalis of Meynert), 34, 83, 86, 306, 538, 540, 545 Nucleus of the solitary tract, 305, 306 Nurr1, 275, 552 Obesity, 244 Object retrieval test, 412 Observational rating scales, 242 Occipital cortex, 73, 78–83, 530, 536–542 Oculomotor nerve, 10, 15 Olfactory bulb, 24, 48, 54, 65, 68, 71–74, 78, 84, 119, 529 Olfactory deficits, 112 Olfactory epithelium, 25, 111, 113 Olfactory tubercle, 22, 45, 48, 52–55, 62, 68–79, 84, 86, 154, 155, 159, 166, 170, 240, 267, 303, 304, 322, 332, 343 Index On-Off fluctuations, 266 Open field, 157, 166–169, 273, 274, 278 Opiates, 46, 109, 154, 163, 164, 278, 322, 330, 337–341, 354, 362, 478, 489–492 Opioid receptor, 473, 480–485, 489–491, 494–496 Delta, 473, 481–485, 495 Kappa, 473, 480–485, 489, 494, 495 Mu, 480, 481–485, 489, 491, 494–496 Opossum, 17, 19 Opponent process theory, 362 Optic chiasm, 437, 443 Optimal foraging, 414 Orbitofrontal cortex, 46, 69, 353, 397, 406, 417, 532–538, 545, 550, 555 Osmotic regulation, 245, 442, 455–457, 496 Ovariectomy, 459, 466, 467, 476, 479, 485–489 Oxidative stress, 270, 271 Oxytocin, 443, 452, 455–458, 489, 491, 492, 495 Palatability, 244, 318, 348–350, 362, 372, 398 Pallidothalamic projections, 41, 42 Paracrine regulation, 455, 473, 478 Paraquat, 272 Parasynaptic actions, 50 Pargyline, 246, 251 Parietal cortex, 68–72, 77–80, 84, 88, 155, 530, 533, 536, 540, 555 Parkinson’s disease, vii, 3, 5, 28, 32, 37, 40, 43, 63, 65, 76, 88, 89, 109, 110, 153, 154, 171, 181, 182, 227, 237–240, 246, 250, 254, 259, 263, 266–272, 278, 279, 395, 409, 412, 416–422, 435 Partial lesions, 175, 177, 181, 182, 249 Parturition, 455, 491 Parvalbumin, 31, 32, 71, 73, 77 Passive avoidance, 251, 271, 277, 333 Pavlovian learning, 303, 308–311, 318–335, 350–353, 364–372, 399–403, 415 Paw reaching, 3, 41, 44, 48, 51, 65, 124, 177, 242, 252, 261, 262, 268–274, 307, 412 PD128907, 539, 543, 544 PE2I, 539, 547 Pedunculopontine nucleus, 29, 40–44 Pentylenetetrazol, 357 Perforant path, 65, 534, 547 Performance-related impairments, 259, 313, 315, 326, 327 Pergolide, 257, 421 Perirhinal cortex, 61, 63, 74, 78 Periventricular dopamine neurons, 438, 442–451, 455–468, 472, 476–485, 496 Periventricular-hypophysial dopamine neurons, 438, 442–457, 465, 466, 471–495 Perseveration, 266, 411 Pertussis toxin, 121–132, 161, 162, 166 Phaclophen, 486 Phagocytosis, 28 Phasic firing (see also Electrophysiology), 212, 213, 224, 226, 243, 319, 348–354, 360, 396, 399, 423, 463, 479 Phencyclidine, 257, 343, 354 Phenothiazines, 239 Phenotype, 37, 61, 113, 128, 158, 162, 167–170, 176, 177, 182, 183, 273–277, 442, 444, 476, 526 Phenylethanolamine-N-methyltransferase (PNMT), 445 Phosphatidyl inositol, 474 Phosphodiesterase, 112, 114 Phospholipase C, 121, 126–130, 155, 161 Phospholipase D, 162 Photocell recording, 241, 264 Picrotoxin, 331, 357 Pig, 269, 486, 491 Piloerection, 246 Pimozide, 239, 313, 318, 320, 326–329, 339, 341, 401 Pineal gland, 488 Pinealectomy, 490 Piriform cortex, 53, 62–64, 68–71, 74, 78, 84, 154 Pituitary gland, 67, 74, 76, 80, 84, 86, 110, 124–130, 161, 162, 435–437, 440–495 Anterior lobe, 74, 125, 440, 443, 447, 448, 452–481, 485–495 Intermediate lobe, 74, 76, 437, 441, 442, 448, 451–454, 471, 476, 479–483, 487, 493–495 Posterior (neural) lobe, 437, 441–444, 451–458, 471–476, 480–495 Pituitary hormones, 435, 436, 442, 452, 457, 473, 477, 483, 485, 494 Pituitary lesions, 463–471 Place preference (see also Conditioned place preference), 277 Placenta, 491 Planning (see also Executive function), 40, 154, 415–421 Plasma membrane, vii, 31, 55, 73 583 Index Plasticity, ix, 37, 56, 110, 117–121, 133, 137, 182, 183, 199, 216, 222–225, 237, 240, 248–253, 274, 365, 397 Polymerase chain reaction, 37, 51, 133, 214 Pons, 155, 538 Positron emission tomography (PET), 266, 345, 354, 416–421, 525, 526, 548–554, 558 Postnatal mortality, 162 Postsynaptic striatal neurone, 249 Posture, 162, 255, 259, 267–270 Potassium channels, 74, 120, 125, 126, 130, 155, 161, 179, 21–220, 224, 273, 486 Prefrontal cortex, 20, 29, 33, 43, 46, 53, 55, 59–64, 68–79, 83, 86, 109, 120, 203, 240, 303–306, 325, 326, 336, 339, 343, 348–357, 362, 369, 397–400, 406–425, 532–538, 542–550, 555, 556 Pregnancy, 453, 463, 467, 470, 485–493 Premature responding, 264 Premotor cortex, 42–46, 63, 533 Preproenkephalin, 68 Prepulse inhibition, 84, 170, 253, 276, 277, 403, 405 Primates, 1, 2, 9, 13, 17–21, 29, 31, 38–46, 52, 53, 60–64, 73, 78–88, 110, 175, 203, 210, 211, 240, 254, 266–271, 319, 339–358, 367, 396, 398, 403–420, 424, 491, 526–534, 538, 540, 545–554 Priming, 122, 252, 257, 324, 325 Prodynorphin, 482, 538, 554 Proenkephalin, 484, 485, 540, 554 Proestrus, 458, 476, 487–491 Progesterone, 439, 466, 476, 487–491, 496 Progressive ratio schedule of reinforcement, 164, 337–339, 366 Prolactin, 110, 125, 127, 436, 440–444, 448, 452, 453, 457–495 Prolactin receptor, 466, 467, 491–493 Proopiomelanocortin (POMC), 442, 452–454, 481–487, 494, 495 Prostaglandin, 270, 490 Protein kinase A, 112–125, 134, 155, 160, 444 Protein kinase C, 115–122, 127–132, 155, 161, 162, 274, 469, 474, 475 Protein phosphatase (see also Calcineurin), 10–14, 112–127 Prus, Jan, 38 Psychiatric disorders, ix, 2, 30, 54, 57, 61, 63, 77, 89, 109, 137, 356, 364, 525, 526, 538, 548, 551, 558 Psychomotor retardation, 556 584 Psychosis, 168, 170, 253, 395, 411, 417, 419, 552 Psychostimulants (see also Amphetamine), 33, 55–59, 109, 132–136, 169, 227, 311, 322, 325, 330, 331, 338, 341–345, 354–358, 361, 365–368, 395, 404, 409, 420, 548–551 Puberty, 435–441 Purkinje cells, 80, 273 Putamen (see also neostriatum), 38, 39, 45, 46, 73, 74, 78, 79, 83, 124, 154, 238, 240, 266, 267, 348, 354, 355, 417, 530, 531, 536–551, 556 Pyramidal neuron, 61, 64, 73, 84, 88, 541, 545 Pyramidal tract, 43 Quinelorane, 166, 451 Quinine, 313, 349, 350, 351 Quinpirole, 126, 129, 160, 164–167, 178, 181, 219, 257, 323, 325, 401–403, 451 Rabbit, 36, 237, 238, 326, 491 Raclopride, 134, 263, 313, 321, 325, 329, 344, 348, 354, 421, 451, 544, 548, 549 Radar tracking, 241 Radial maze, 335, 336, 402, 410–413 Radiofrequency lesions, 243 Raised beam, 260 Raphe´ nucleus, 4, 9–14, 30, 44, 52, 74, 409, 538 Rapid Eye Movements (see also Sleep), 33–35 Ras, 127, 130, 134 Rat, 1–88, 110, 127, 131, 134, 155, 159, 161– 163, 172, 176, 178, 209–212, 218, 225, 226, 237–274, 313–315, 319–361, 366–372, 397–415, 424, 435–439, 443–446, 453–457, 463–473, 479–494, 531, 535, 536, 544, 553 Rat strains, 471 Ratio schedules of reinforcement, 164, 262, 263, 309, 314, 321, 324, 338–340, 358 Reaction time, 263–271, 311, 403, 405 Rearing, 157, 166–169, 256, 273, 277, 278, 315, 332 Reboxetine, 342 Receptor autoradiography, 30, 37, 68–86, 167, 238, 240, 249, 256, 257, 274, 421, 452, 477, 484, 539–550, 554–556 Recovery of function, 28, 177, 237, 244–253, 260, 264, 267–271, 340, 351, 363, 551–553, 557, 558 Index Red nucleus, 3, 4, 10–14, 36 Reference memory, 410 Regenerative sprouting, 173, 175, 250, 254 Regulatory impairments, 244, 247 Reinforcers (see also Reward), 60, 135, 154, 164, 225, 303, 307–309, 312, 316, 321–330, 333, 337–344, 352, 354, 357, 361–366, 373, 395–401, 404, 405, 549 Remoxipride, 451 Reserpine, 135, 169, 237–239, 322 Resting tremor, 43, 267 Restraint stress, 493, 494 Reticular formation, 441 Retina, 68, 84, 86, 110, 124, 131, 155, 177, 479 Retrograde degeneration, 3, 254 Retrograde tract tracing, 6, 21, 33, 46, 49, 52, 57, 60, 65, 442 Reversal learning, 83, 406, 417, 418, 422, 548 Reward (see also Reinforcers), ix, 1, 53–56, 65, 71, 77, 88, 110, 133, 137, 154, 157, 164, 168, 169, 183, 199, 210–213, 216, 224–226, 245, 251, 258, 262, 277–279, 303–373, 396, 397, 403, 418, 525, 548, 556 Ribosomes, 13 Righting response, 260, 261, 274, 275 Rigidity, 43, 241, 259, 266–270, 273 Rotarod, 169, 170, 260, 271, 277 Rotation, 180, 182, 254–260, 274 Rotenone, 28, 254, 272 Rough endoplasmic reticulum, 13 RTI-55, 557 Runway, 314–317 Saccadic eye movements, 319, 320, 411, 414, 421 Saccharine, 164, 313, 334, 341, 351 Satiety, 314, 349, 477 Scaffolding proteins, 115 SCH-23390, 121, 123, 134, 155, 160, 170, 216, 217, 223, 225, 252, 263, 313, 315, 319, 321, 325, 326, 329–335, 339–343, 357, 406, 412–414, 555, 557 SCH-39166, 171, 331–335 Schizophrenia, 54, 57, 61, 84, 89, 109, 153, 239, 252, 253, 395, 404–406, 409, 416, 419, 425, 435, 554–558 Scouten knife, 254 Second-order schedules of reinforcement, 336, 352, 358, 401 Secretin, 34 Selenium, 271 Self-administration, 163, 164, 212, 266, 321, 324, 325, 336–344, 352–368, 400, 548, 550, 554 Self-mutilation, 252 Sensitization, 56, 68, 160, 359, 365–372 Sensorimotor gating, 59, 88, 170, 251, 253, 276, 405, 423, 480 Sensorimotor impairment, 246, 250, 260, 261 Sensory inputs, 253 Sensory preconditioning, 399, 401 Septum, 22, 55, 58–62, 68, 69, 74, 80, 83, 154, 240, 253, 306, 438, 542, 545 Serotonin, 6, 20, 30, 34, 35, 52, 159, 160, 175, 245, 251, 257, 267, 273, 306, 342, 409, 410, 421, 425, 454, 464, 465, 482, 489, 490, 494, 556, 557 Serotonin receptor, 30, 159, 342, 489, 494 Set-shifting tests, 407, 415–417, 420, 421 Sex differences, 438–440, 454, 465, 470–476, 480, 481, 484, 488, 494, 495 Sexual behaviour, 213, 245, 304, 307, 316, 320, 329, 366, 372, 472 Sexually dimorphic nucleus, 439–443, 496 Sheep, 435–438, 442, 443, 456, 459, 467, 470, 491 Short-term memory, 333–336, 410 Shuttle box, 170 Side bias, 257, 259, 265 Signal detection theory, 263 Signal transduction, ix, 2, 109–111, 116, 121–125, 128–133, 166, 168, 474 Simple reaction time, 263, 266 Single Photon Emission Tomography (SPECT), 525, 526, 556, 558 Single-trial tests, 332–335, 369 SKF-38393, 121, 123, 160, 217, 219, 257, 321, 323, 402, 406, 451 SKF-81297, 170, 413 SKF-82958, 323 Skilled forelimb reaching, 251 Skinner, B.F., 308, 459 Sleep, 33, 34, 35, 276, 459 Smoking, 344 Sniffing, 157, 159, 168, 242–244 Social dominance, 550 Social isolation, 405 Social stress, 276, 493, 550 Sodium channels, 118 Somatostatin, 46, 459462, 477, 478, 496 Somatotroph, 459, 460, 477, 478 Soămmerring, Samuel Thomas von, Somnolence, 247 585 Index Sonic hedgehog, 275 Spatial deficits, 273 Spatial memory, 158, 335, 402, 403, 409–424 Spinophilin, 117–121, 127, 555 Spiroperidol, 239, 326 Spontaneous alternation, 410 Spontaneous behaviour, 157, 277 Spontaneous rotation, 258 Sprouting, ix, 153, 171–177, 182, 183, 250, 251 Stages of recovery, 244, 247 Staircase test, 261, 262, 268 State dependency, 33–35, 227, 327–329, 363 Stem cell, 34, 65, 177, 179, 182 Stepping test, 260 Stereology, 158, 172, 203 Stereotaxic surgery, 9, 40, 238, 243, 253, 254, 268, 311 Stereotypy, 241–243, 251, 252, 477 Steroid hormones, 438–440, 443, 454, 458, 465, 471, 472, 476, 480, 485, 488, 489, 496 Sticky label test, 260 Stimulus-bound behaviours, 244, 318–321, 329, 350 Stress, 252, 270, 274, 276, 396, 400, 414, 415, 426, 445, 453, 454, 463–467, 471–474, 478, 481, 487–495 Stria medullaris, 57 Stria terminalis, 57, 62, 303, 306, 335, 357, 533, 547 Striatal lesions, 3, 240, 262 Striatal topography, 243, 253, 262, 263 Striatonigral projections, 11, 28, 39, 41–45, 50, 51, 76, 116, 156, 200, 202, 214 Striatopallidal projections, 39–45, 51–59, 115, 156, 159, 534, 554 Striatum (see also Neostriatum), 2–7, 13, 21–32, 35, 38–63, 68, 70, 73, 76–79, 86, 109–128, 132–136, 155–183, 199–213, 218, 223–227, 237–242, 248–251, 255–258, 262–274, 278, 279, 303, 306, 319–322, 336, 344, 345, 354, 355, 367, 368, 395–397, 402, 403, 412, 417–423, 481, 485, 529–557 Striosomes, 32, 39, 45–47, 50, 53, 74, 83, 86, 531–547 Stromal cell-derived factor (SDF-1), 37 Stroop test, 421 Subiculum, 53, 62, 65, 69, 73, 74, 78, 88, 306, 335, 336, 413, 534, 541, 543, 547 Substance P, 33, 46, 51, 68, 71, 76, 80, 82, 135, 136, 156, 159, 163, 167, 168, 538 Substantia innominata, 57, 58, 68, 69, 529, 533 586 Substantia nigra, 1–86, 109, 110, 116, 125, 154–156, 163–165, 183, 206, 224, 225, 240, 248, 250, 253, 267–275, 278, 319, 436, 439, 467, 470, 485, 527–547, 553 Dorsal and ventral tiers, 1, 7, 9, 13, 21–24, 32, 37–41, 47–50, 56, 172, 527–535, 540, 543, 546, 553 Parabrachial nucleus, 9–11, 20, 44, 69, 74, 305, 306, 527, 528, 534 Paranigral nucleus, 9, 11, 14, 527, 528 pars compacta, 3, 6–84, 109, 154, 166, 171–183, 201, 209, 224, 355, 527, 528, 540, 545, 546 pars reticulata, 6, 11–45, 68–70, 74, 77, 86, 88, 156, 163, 319, 527, 528, 538, 540, 545 Retrorubral area, 1, 9, 16, 20, 48, 49, 61, 80, 253, 272, 527, 534, 546 Substantia nigra lesions, 5, 70, 174, 257 Substitution of function, 251 Subthalamic lesions, 260–266 Subthalamic nucleus, 29, 43, 52, 156, 163, 260–266, 269, 435, 494, 533 Subventricular zone, 65 Suckling, 275, 453, 457, 467, 470, 476, 481, 482, 485, 488, 492–495 Sucrose, 313, 314, 318, 327, 329, 334, 335, 341, 348–354, 366, 403, 404 Sulpiride, 110, 160, 315, 329–334, 341, 402, 403, 406, 412, 421 Superior cervical ganglion, 110, 442 Superior colliculus, 36, 40, 42, 69, 80, 545 Supersensitivity, 240, 249–252, 256, 257, 276 Supplementary motor cortex, 42, 46, 63 Swallowing, 314 Swimming, 157, 273, 274, 277, 323, 403, 493 Symmetric synapses, 29, 50, 55, 63, 70, 73, 76, 200–207, 485 Sympathetic nervous system, 171, 245, 275, 277, 464, 472 Synapse, 17, 24–26, 29, 50, 55, 63, 68, 70, 73, 76, 85, 110, 115, 120, 171, 174–177, 181, 183, 199–209, 216, 222–227, 239, 249, 257, 274, 276, 319, 397, 398, 440, 446, 447, 453, 464, 480, 494, 496, 529, 545, 547 Synaptic vesicles, vii, 24, 25, 29, 31, 51, 73, 85, 124, 181, 201–203, 241, 257, 276, 322, 446–448, 456, 473, 547, 548, 553 Synaptophysin, 81 Synaptosomes, 178, 181, 249 Index T cells, 37 T maze, 271 Tachykinin, 133, 538 Tail of caudate, 46, 537 Tail pinch, 351 Tardive dyskinesia, 182, 555 Taste, 305–308, 313, 314, 318, 329, 333–337, 345, 348–352, 362, 369, 398, 404 Temporal cortex, 57, 62, 79, 83, 86, 530, 536–542, 555 Terminal arborisation, 50, 171–175, 179, 250 Terminal lesions, 253, 254, 265 Testosterone, 439, 442, 470–472, 493 Tetra-ethyl ammonium, 220, 224 Tetrodotoxin, 217, 219, 468 Thalamocortical projection, 34, 39, 41, 42, 54, 56, 64, 545 Thalamostriatal projection, 39- 41, 46 Thalamus, 14, 39–42, 54, 58–60, 68, 72, 74, 80, 84, 86, 155, 156, 218, 305, 436, 441, 530, 534–547 Centromedian/parafascicular nucleus, 40, 41, 86, 541, 545 Interfascicular nucleus, 9–16, 57 Interstitial nucleus, 10, 12 Intralaminar nuclei, 39–41, 52, 53, 541 Lateral geniculate nucleus, 60, 78, 80, 479, 541, 543 Medial geniculate nucleus, 69, 541–543 Mediodorsal nucleus, 54, 83, 530, 534, 537, 541–543, 547 Midline nuclei, 41, 53 Paraventricular nucleus, 53–60, 64, 441, 445, 455, 463 Pulvinar, 537, 541–543 Reticular nucleus, 12, 41, 42, 86, 542, 545 Ventral anterior/ventral lateral nuclei, 39, 42, 60, 69, 534, 541 Ventromedial nucleus, 42 Thermoregulation, 247, 248 Thirst, 245 Thorndike, Edward L., 309 Thyroid gland, 461–465 Thyroid lesions, 462, 463 Thyrotroph, 461, 462 Thyrotropin, 452, 461–468, 473, 477 Thyrotropin releasing hormone, 461–463, 489, 491 Thyroxine, 461, 467 Tolerance, 359, 362–365, 476 Tongue, 124, 313, 314, 396 Tonic firing and release, 127, 212–215, 321, 360, 363, 399, 423, 454, 466, 469, 472, 478, 479, 487, 488, 490, 491, 495, 496 Tourette syndrome, 153 Tower of London task, 420 Transcription factors, 114, 132–134, 137, 440, 449 Transgenic animals, ix, 2, 127, 128, 135, 153–185, 252, 275–279 Transplantation, 182, 250, 256, 260, 273, 453 Treadmill, 259 Tremor, 266–270, 273 Trigeminal nucleus, 44 Triiodothyronine, 461 Tsai, C., 17, 19 Tuberoinfundibular dopamine neurons, 436–453, 457–495 Turning on inclined grid, 260 Tyrosine hydroxylase, 7–37, 44, 50, 52, 56, 57, 60, 63, 71, 73, 77, 80, 85, 128, 162, 165, 169–181, 200–202, 206, 239, 248, 250, 258, 271–276, 313, 350, 438–451, 456, 460, 466–470, 474–476, 481–492, 526–533, 552–556 U maze, 326 Ubiquitin, 278 UH-232, 166 Unconditioned stimuli, 303, 308, 309, 324–328, 333–335, 402 United Parkinson’s Disease Rating Scale (UPDRS), 268 Varicosities, 48–50, 61, 171, 172, 176, 200–204, 533, 556 Vasoactive intestinal polypeptide (VIP), 479, 489, 491 Vasopressin, 442, 443, 452, 455–457, 464, 482, 484, 495, 496 Ventral mesencephalon (see also Substantia nigra, Ventral tegmental area), 109, 210, 238, 246, 275 Ventral pallidum, 29, 40, 53–59, 62, 68, 69, 74, 83, 306, 533 Ventral striatum (see also Nucleus accumbens), 20, 38, 42, 45–55, 79, 82, 83, 111, 131, 154, 160, 167, 183, 238–243, 253, 257, 271, 274, 303–306, 317, 318, 322, 354, 355, 368, 397–399, 404, 412, 417, 421, 529–533, 538, 542–555 587 Index Ventral tegmental area (VTA), 1, 9–37, 44, 48–68, 74, 75, 80, 83, 86, 109, 154, 160, 163, 166, 240, 253, 270–274, 306, 325, 342, 343, 350–355, 436, 527–534, 546, 547 Vesicular acetylcholine transporter, 29 Vesicular monoamine transporter (VMAT), 25, 276, 553 Vesicular release, 241 Vicq d’Azir, Felix, 3, 45 Vigilance, 406, 420 Visual discrimination learning, 265, 401, 417 Voltage sensitive ion channels, vii, 25, 131, 218, 221, 223 Volume transmission, 25, 207, 423, 533 Voluntary behaviour, 53, 154, 244, 259, 277, 279 von Frey hairs, 403 Water maze, 157, 158, 170, 251, 271, 277, 279, 402, 403 Watson, John B., 309 Wearing off effects, 238 Weaver strain, 32, 272, 273 Weight loss, 246 Win-stay and win-shift tasks, 402, 410, 413 Wisconsin card sorting test, 406, 416, 420–424 Withdrawal, 163, 265, 325, 362, 363, 417, 554 588 Working memory, 63, 71, 335, 395, 396, 409–425, 555 Xenopus, 118, 119, 129–131, 165 Y maze, 276, 326 Yerkes-Dodson hypothesis, 412–418, 422 Zona incerta, 10, 12, 40, 69, 74, 76, 436–445, 451, 455, 458, 465–467, 470, 476, 479, 481, 487, 495 a-Melanocyte stimulating hormone, 442, 453, 454, 457, 476, 479, 483, 487, 493–495 a-Methyl-para-tyrosine, 322 a-Methyl-p-tyrosine, 223, 237, 239, 248, 252, 257, 258, 265, 322, 447, 448, 465, 466, 478 a-Synuclein, 278, 279 b-Carbolines, 357 b-Endorphin, 444, 453, 480–495 g-Aminobutyric acid (GABA), 28, 32, 33, 45, 119, 163, 167, 205, 206, 306, 319, 337, 425, 454, 480, 485–489, 494, 496, 542, 545 g-Hydroxybutyrolactone, 451 ... Hoăkfelt et al. , 1983; Skirboll et al. , 1984 ), also at the ultrastructural level (see Smith et al. , 1998; Sesack, 2003) Last but not least, altogether, these studies inspired the series of the Handbook. .. fasciculus retroflexus; GC, griseum centralis; LM, lemniscus medialis; NIP, nucleus interpeduncularis; NR, nucleus ruber; SNC, substantia nigra, zona compacta; SNL, substantia nigra, pars lateralis; SNR,... Dopamine- dependent plasticity of corticostriatal synapses 3.4 Structural plasticity Synthesis and conclusions References V MOTOR FUNCTION (S) OF THE NIGROSTRIATAL DOPAMINE SYSTEM: STUDIES OF LESIONS AND BEHAVIOR