The Dopamine Receptors T HE R ECEPTORS KIM A NEVE, SERIES EDITOR The Dopamine Receptors, Second Edition, EDITED BY Kim A Neve, 2010 Functional Selectivity of G Protein-Coupled Receptor Ligands: New Opportunities for Drug Discovery, EDITED BY Kim A Neve, 2009 The Cannabinoid Receptors, EDITED BY Patricia H Reggio, 2009 The Glutamate Receptors, Swanson, 2008 EDITED BY Robert W Gereau, IV, and Geoffrey T The Chemokine Receptors, EDITED BY Jeffrey K Harrison, 2007 The GABA Receptors, Third Edition, 2007 EDITED BY S J Enna and Hanns Möhler, The Serotonin Receptors: From Molecular Pharmacology to Human Therapeutics, EDITED BY Bryan L Roth, 2006 The Adrenergic Receptors: In the 21st Century, 2005 EDITED BY Dianne M Perez, The Melanocortin Receptors, EDITED BY Roger D Cone, 2000 The GABA Receptors, Second Edition, Bowery, 1997 EDITED BY S J Enna and Norman G The Ionotropic Glutamate Receptors, EDITED BY Daniel T Monaghan and Robert Wenthold, 1997 The Dopamine Receptors, EDITED BY Kim A Neve and Rachael L Neve, 1997 The Metabotropic Glutamate Receptors, EDITED BY P Jeffrey Conn and Jitendra Patel, 1994 The Tachykinin Receptors, EDITED BY Stephen H Buck, 1994 The Beta-Adrenergic Receptors, EDITED BY John P Perkins, 1991 Adenosine and Adenosine Receptors, EDITED BY Michael Williams, 1990 The Muscarinic Receptors, EDITED BY Joan Heller Brown, 1989 The Serotonin Receptors, EDITED BY Elaine Sanders-Bush, 1988 The Alpha-2 Adrenergic Receptors, EDITED BY Lee Limbird, 1988 The Opiate Receptors, EDITED BY Gavril W Pasternak, 1988 Kim A Neve Editor The Dopamine Receptors Editor Kim A Neve Portland VA Medical Center Oregon Health & Science University 3710 SW US Veterans Hospital Rd Portland, OR 97239-2999 USA nevek@ohsu.edu ISBN 978-1-60327-332-9 e-ISBN 978-1-60327-333-6 DOI 10.1007/978-1-60327-333-6 Library of Congress Control Number: 2009937456 © Humana Press, a part of Springer Science+Business Media, LLC 2010 All rights reserved This work may not be translated or copied in whole or in part without the written permission of the publisher (Humana Press, c/o Springer Science+Business Media, LLC, 233 Spring Street, New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights While the advice and information in this book are believed to be true and accurate at the date of going to press, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made The publisher makes no warranty, express or implied, with respect to the material contained herein Printed on acid-free paper springer.com Preface As sites of action for drugs used to treat schizophrenia and Parkinson’s disease, dopamine receptors are among the most validated drug targets for neuropsychiatric disorders Dopamine receptors are also drug targets or potential targets for other disorders such as substance abuse, depression, Tourette’s syndrome, and attention deficit hyperactivity disorder When chapters were being written for the first edition of “The Dopamine Receptors,” published in 1997, researchers were still coming to grips with the discovery of novel dopamine receptor subtypes whose existence had not been predicted by pharmacological analysis of native tissue Although we are still far from a complete understanding of the roles of each of the dopamine receptor subtypes, the decade since the publication of the first edition has seen the creation and characterization of mice deficient in each of the subtypes and the development of increasingly subtype-selective agonists and antagonists Many of the chapters in this second edition rely heavily on new knowledge gained from these tools, but the use of knockout mice and subtype-selective drugs continues to be such a dominant theme in dopamine receptor research that these topics are also discussed in standalone chapters The field of G protein-coupled receptors has advanced significantly since the publication of the first edition, with a model of GPCR signaling based on linear, compartmentalized pathways having been replaced by a more complex, richer model in which neurotransmitter effects are mediated by a signalplex composed of numerous signaling proteins, including multiple GPCRs, other types of receptors, such as ionotropic receptors, accessory and scaffolding proteins, and effectors Again, although many chapter topics are affected by this more complex model, key aspects of the model are specifically addressed in new chapters on dopamine receptor-interacting proteins and on dopamine receptor oligomerization My goal has been to produce a book that will serve as a reference work on the dopamine receptors while also highlighting the areas of research that are most active today To achieve this goal, I encouraged contributors to write chapters that set a broad area of research in its historical context and that look forward to new research opportunities I hope that readers will agree with me that the authors have achieved that goal Portland, Oregon March, 2009 Kim A Neve v Contents Historical Overview: Introduction to the Dopamine Receptors Philip Seeman Gene and Promoter Structures of the Dopamine Receptors Ursula M D’Souza 23 Structural Basis of Dopamine Receptor Activation Irina S Moreira, Lei Shi, Zachary Freyberg, Spencer S Ericksen, Harel Weinstein, and Jonathan A Javitch 47 Dopamine Receptor Subtype-Selective Drugs: D1-Like Receptors David E Nichols 75 Dopamine Receptor Subtype-Selective Drugs: D2-Like Receptors Olaf Prante, Miriam Dörfler, and Peter Gmeiner 101 Dopamine Receptor Signaling: Intracellular Pathways to Behavior Robert J Romanelli, John T Williams, and Kim A Neve 137 Dopaminergic Modulation of Glutamatergic Signaling in Striatal Medium Spiny Neurons Weixing Shen and D James Surmeier 175 Regulation of Dopamine Receptor Trafficking and Responsiveness Melissa L Perreault, Vaneeta Verma, Brian F O’Dowd, and Susan R George Dopamine Receptor-Interacting Proteins Lisa A Hazelwood, R Benjamin Free, and David R Sibley 10 Dopamine Receptor Oligomerization Kjell Fuxe, Daniel Marcellino, Diego Guidolin, Amina Woods, and Luigi Agnati 193 219 255 vii viii 11 12 13 14 Contents Dopamine Receptor Modulation of Glutamatergic Neurotransmission Carlos Cepeda, Véronique M André, Emily L Jocoy, and Michael S Levine Unraveling the Role of Dopamine Receptors In Vivo: Lessons from Knockout Mice Emanuele Tirotta, Claudia De Mei, Chisato Iitaka, Maria Ramos, Dawn Holmes, and Emiliana Borrelli Dopamine Receptors and Behavior: From Psychopharmacology to Mutant Models Gerard J O’Sullivan, Colm O’Tuathaigh, Katsunori Tomiyama, Noriaki Koshikawa, and John L Waddington Dopamine Modulation of the Prefrontal Cortex and Cognitive Function Jeremy K Seamans and Trevor W Robbins 15 In Vivo Imaging of Dopamine Receptors Anissa Abi-Dargham and Marc Laruelle 16 Dopamine Receptors and the Treatment of Schizophrenia Nathalie Ginovart and Shitij Kapur 17 Dopamine Receptor Subtypes in Reward and Relapse David W Self 18 Dopamine Receptors and the Treatment of Parkinson’s Disease Eugenia V Gurevich and Vsevolod V Gurevich 19 281 303 323 373 399 431 479 525 Dopamine Receptor Genetics in Neuropsychiatric Disorders Frankie H.F Lee and Albert H.C Wong 585 Index 633 Contributors Anissa Abi-Dargham Division of Translational Imaging, Departments of Psychiatry and Radiology, Lieber Center, Columbia University College of Physicians and Surgeons, NY 10032, USA, aa324@columbia.edu Luigi Agnati Department of Biomedical Sciences University of Modena and Reggio Emilia, 41100-Modena, Italy Véronique M André Mental Retardation Research Center, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA Emiliana Borrelli Department Microbiology and Molecular Genetics, 3113 Gillespie Neuroscience Facility, University of California, Irvine, CA 92617, USA, borrelli@uci.edu Carlos Cepeda Mental Retardation Research Center David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA Claudia De Mei Department Microbiology and Molecular Genetics, 3113 Gillespie Neuroscience Facility, University of California, Irvine, CA 92617, USA Miriam Dörfler Department of Chemistry and Pharmacy, Friedrich Alexander University Erlangen-Nürnberg, 91052 Erlangen, Germany Ursula M D’Souza MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, King’s College, London, UK, ursula.d’souza@iop.kcl.ac.uk Spencer S Ericksen Department of Physiology and Biophysics, Weill Medical College of Cornell University, New York, NY 10021, USA R Benjamin Free Molecular Neuropharmacology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 30852, USA Zachary Freyberg Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA ix x Contributors Kjell Fuxe Department of Neuroscience, Karolinska Institutet, 17177-Stockholm, Sweden, kjell.fuxe@ki.se Susan R George Departments of Pharmacology and Medicine, King’s College Circle, Centre for Addiction and Mental Health, University of Toronto, Toronto, ON M5S 1A8, Canada, s.george@utoronto.ca Nathalie Ginovart Neuroimaging Unit, Department of Psychiatry, University of Geneva, Geneva, Switzerland, nathalie.ginovart@unige.ch Peter Gmeiner Department of Chemistry and Pharmacy, Friedrich Alexander University Erlangen-Nürnberg, 91052 Erlangen; Laboratory of Molecular Imaging, Clinic of Nuclear Medicine, Friedrich Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany, gmeiner@pharmazie.uni-erlangen.de Diego Guidolin Section of Anatomy, Department of Human Anatomy and Physiology, University of Padova, 35121-Padova, Italy Eugenia V Gurevich Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA, eugenia.gurevich@vanderbilt.edu Vsevolod V Gurevich Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA Lisa A Hazelwood Section of Molecular Neuropharmacology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20852, USA Dawn Holmes Department of Microbiology and Molecular Genetics, 3113 Gillespie Neuroscience Facility, University of California, Irvine, CA 92617, USA Chisato Iitaka Department Microbiology and Molecular Genetics, 3113 Gillespie Neuroscience Facility, University of California, Irvine, CA 92617, USA Jonathan A Javitch Center for Molecular Recognition, Columbia University College of Physicians and Surgeons, NY 10032, USA, jaj2@columbia.edu Emily L Jocoy Mental Retardation Research Center, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA Shitij Kapur Department of Psychological Medicine, Institute of Psychiatry, London, UK Noriaki Koshikawa Department of Pharmacology, Nihon University School of Dentistry, Tokyo, 101, Japan Marc Laruelle Schizophrenia and Cognitive Disorder Discovery Performance Unit, Neurosciences Center of Excellence in Drug Discovery, GlaxoSmithKline, Harlow, UK Frankie H.F Lee Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, ON M 5A 4R4, Canada Index A A2A /D2 heteromer, in striato-pallidal GABA pathway, 264–265 Abbott isochromans chroman molecules, 83 D1 agonist ligands, 83 D1 and D2 affinities, 82 Abi-Dargham, A., 399–418, 448 Abnormal involuntary movements (AIMs), 550–551 suppression of, 552 ABT-724, D4 agonists, 116 ABT-431, O,O-diacetyl prodrug, 82 Accili, D., 346 Activator protein-1 (AP-1) transcription, 535 A-220528, D4 agonists, 118 A-412997, D4 agonists, 117 A-381393, D4 antagonists, 121 Adenylate cyclase, 140 D1 and D2 receptors, 75 D1-like receptor regulation of, 140–142 D2-like receptor regulation of, 142 type KO mice, 143 regulation by G protein-coupled dopamine receptors, 139–140 Adrenoceptors, 48–49 Agid, O., 448 Agnati, L., 255–273 Agonist-induced M3R activation, 54 Akt/GSK-3β pathway, 151–152 Akt1 KO mice, 151 D1-like receptor regulation of, 152 D2-like receptor regulation of, 152–153 Alanine-scanning mutagenesis technique, 53 Albert, H C., 585–619 Albin, R L., 176 Alcohol consumption dopamine receptor subtypes modulation of, 506–507 quinpirole drug, infusions, 498–499 ALG-2-interacting protein (AIP1), 231–232 α-Amino-3-hydroxy-5-methyl-4-propionate (AMPA) receptors, 245, 282, 287 and DA receptors, 284–288 Aminoindans, 107 Aminomethylfluorenes, 86 Aminotetralins arylcarboxamidobutyl substituted, 108–109 2-methoxybenzamides and analogs, 108 binding affinities of, 105 conformers, 104 design of, 104 side chain variations in, 105 Amisulpride, 102, 453 in schizophrenia therapy, 436 Amphetamine drug, 312, 380, 485, 492 And´en, N E., Andr´e, V M., 281–295 Ankyrin repeat and kinase domain containing (ANKK1) gene, 596 Antipsychotics, 435–437 atypical derivatives, 102, 436–437 classical family of, 102 dopamine turnover and, 8–9 haloperidol to dopamine D2 receptors, binding, history of, 1–2 membrane stabilization by, 2–4 therapeutic concentrations of, See also Schizophrenia Apokyne c , 77 See also Apomorphine drug Apomorphine drug and climbing behavior, 440–441 as rescue medication for Parkinson patients, 77 structure of, 76, 492 Aripiprazole, 102, 210 K.A Neve (ed.), The Dopamine Receptors, The Receptors, DOI 10.1007/978-1-60327-333-6, C Humana Press, a part of Springer Science+Business Media, LLC 2010 633 634 Index Armstrong, D., 259 Arrestin, 238 arrestin-dependent signaling, 146–147 Arrestin3 gene, 153 KO mice, 147 Attention deficit hyperactivity disorder (ADHD), 34, 410, 588 Autoreceptors, 155–158 D2-like receptors as, 155–156 D2 receptor as, 156–158 expression, 155 Avale, M E., 356 Avlani, V A., 53 stimulation reward, modulation, 488 AMPA glutamate receptor, 490 intracranial infusion studies, 489–490 studies, 489–490 Brain-derived neurotrophic factor (BDNF), 567 Brock, C., 58 Bromocriptine D2 -like agonist, 385, 485–486, 491, 498 alcohol consumption and, 498 Brugmans, Jo Dr., Burt, D R., 5–6 Butyrophenones, 102 B Back-propagating action potentials (bAPs), 182 Bacterial two-hybrid system, 223–224 β2 Adrenergic receptor (B2AR) crystal structures, 48 high-affinity state of, 52 ionic lock in, 50 non-rhodopsin ECL2 structure and, 54 Ballesteros and Weinstein indexing system, 51 Baneres, J L., 53, 57, 59 Beaulieu, J M., 153 Bender, D., 122 Beom, S., 150 Bergson, C., 378 Bioluminence resonance energy transfer (BRET) technique, 269 Bipolar disorder ADHD, association, 588 DRD4 polymorphisms, association of, 614 PET studies on, 408–409 and schizophrenia case–control studies, 595 clinical pharmacological treatment for, 600 promoter region, study, 614–615 Ser9 Gly polymorphism, association with, 601–605 Blum, K., 596 Borrelli, E., 303–316 Boston, M A., Bovine rhodopsin, 48, 90 Boy, C., 123 Bozzi, Y., 344 Brain dopamine receptors in, 9–11 dopaminergic neurons in, 323–324 C Cabergoline, D2 agonist, 385 Cai, G., 539 Calcineurin, 240 Calcium/calmodulin-dependent kinase II (CaMKII), 143 autophosphorylation, 536 GABAergic transmission, 537 NMDA receptor subunit, 536–537 Calcium-dependent activator protein for secretion (CAPS1), 239 Calmodulin, 240–241 Calnexin, 196–197, 230 cAMP response element-binding protein (CREB), 536 Cannabinoid-1 (CB1) receptor, 56 in schizophrenia treatment, 455–456 Capillary electrophoretic mobility shift assays, 36 Carazolol inverse agonist, 50 C5a receptor (C5aR), 53 Carlsson, A., 9–10, 433, 439 Carta, A R., 353 Carta, M., 353 Catalepsy test, 441 Catecholamine-binding GPCRs, see G protein-coupled receptors (GPCRs) Catechol-O-methyl transferase (COMT), 558 Caudal striatum, DA depletion in, 562 Caveolin-1, 237 Centonze, D., 349 Cepeda, C., 281–295 C-fos expression in brain, 442 Chinese hamster ovary (CHO) cells, 149–150 Chloride intracellular channel (CLIC6), 243 Chlorpromazine, 6, 9, 437, 438, 454 use, history of, Cholecystokinin-8 (CCK-8), and D2 receptor, 262–263 Index Chroman molecules with D1 agonist activity, 83 See also Abbott isochromans c-jun N-terminal kinases (JNKs), 147 Class A receptors, 57 Clozapine, 453 and D4 dopamine receptor, 33 in schizophrenia therapy, 436 Cocaine, 484–485, 492 abuse, molecular imaging studies on cue-induced cocaine craving, 413 DAT occupancy by cocaine, 412–413 DOPA decarboxylase, 412 D2 receptors, 411 stimulant-induced DA release, 411–412 modulation, intracranial administration amygdala infusions, reinstatement, 505 dopamine receptors, direct activation, 503–504 intranucleus accumbens shell infusions of, 504 neocortical dopamine receptors, modulation, 505 Collegium Internationale NeuroPsychopharmacologicum (CINP) and antipsychotics, Combined attention and working memory (CAM) task, 381 Comparative molecular field analysis (CoMFA), 113 Compound 4560, see Chlorpromazine Conditioned avoidance response (CAR) test, 441 Conditioned reward modulation in amygdala, 491 treatment with, 490–491 Cyclic adenosine monophosphate (cAMP) accumulation of, 527 cAMP regulatory element-binding protein (CREB), 142 CREB-induced gene transcription, 140 regulated phosphoprotein, 32 kDa (DARPP-32), 140 D2-like receptor stimulation and, 142 drugs of abuse, and activity of, 141 signaling and locomotor activity, 142–143 Cyclothiazide, 287 D Damian, M., 58 Dandridge, P A., 79 DA–NMDA receptor interactions, 284–285 DAT KO mice, 153 635 D1 dopamine receptor chromosome localization, 37 cloning, 36 Gαolf , elevation of, 542 and high-voltage-activated (HVA) Ca2+ currents, 284 KO mice, 144–146 NMDA activation of, 199 prevalence of, 76 promoter and activator region, 37–38 putative mechanisms, representation of, 533 regulatory region, 38–39 synergism, role of NMDA receptors, inhibition of, 541 priming/reverse tolerance, 540–541 trafficking, and tunicamycin treatment, 198 D2 dopamine receptor cloning, 27 dopaminergic lesion, 539 ERK1/2 activation, 539–540 gene structure, 27–28 isoforms, 28 modulation of glutamate release by, 284–285 molecular evidence for, 537 promoter region and transcriptional regulation, 28–30 regulation by PKC, 203 role in regulation of behavioral flexibility, 384–386 role in schizophrenia, see Schizophrenia signaling pathways, changes in, 538 signaling, RGS-mediated attenuation of, 562 splice variants, 137, 138, 150, 156, 304, 340 functional differences, 142, 149–150, 154, 198 synergism possible role of NMDA receptors, inhibition of, 541 priming/reverse tolerance, 540–541 D3 dopamine receptor, 528, 541 alternative splicing, 31 cloning, 30–31 D3 -receptor ligands, 103 aminoindans, 107 aminotetralins, 104–105 arylcarboxamidobutyl substituted aminotetralins, 108–109 DPAT bioisosteres, 105–107 phenylpiperazines, 109–111 636 D3 dopamine (cont.) radioligand candidates, 112–113 structural hybrids, 111–112 isoforms, 31 pharmacological properties of, 530 promoter and regulatory region, 31–33 D4 dopamine receptor and ADHD, 34, 35 cloning, 33 D4 -selective ligands, 114 D4 radioligands, 122–124 selective D4 agonists, 115–121 gene structure, 33–34 polymorphic forms, 34, 35 promoter and regulatory region, 34–36 D5 dopamine receptor ADHD studies, 615 Caucasian study, 615 case-control, 615, 618 chromosome localization, 37 cloning, 36 desensitization, 202 polymorphisms and neuropsychiatric diseases, 616–617 representation of, 615 studies, 614–615 promoter and regulatory region, 39–40 D1 /D2 receptor synergism models, 154 Delay, J., De Mei, C., 303–316 Dihydrexidine (DHX), 80–81 Dihydroxynomifensine, 79 4-(3 ,4 -Dihydroxyphenyl)tetrahydroisoquinoline (THIQ), 80 Dinoxyline (DNX), 85 D4 knockout mice, 379 D1-like dopamine receptors, 11, 24, 75–76 D1 agonists pharmacophore structure, 86–87 accessory binding region, 94 aromatic rings, orientations of, 89–90 binding site model of, 93 catechol moiety, 87–89 embedded dopamine fragment, 87 linking model to 3D receptor, 90–95 sequence alignment for D1 , D2 , and D5 receptors, 91–92 virtual docking, 91, 93 desensitization, 200–202 dopamine D1 drugs Abbott isochromans, 82–84 aminomethylfluorenes, 86 Index apomorphine, 76–77 benzo[a]phenanthridines, 80–82 dinapsoline, 84 dinoxyline, 85 doxanthrine, 85–86 1-phenyl-3-benzazepines, 77–79 4-phenyltetrahydroisoquinolines, 79–80 gene structure and organization of, 36–37 internalization, 204–206 promoter region of D1 dopamine receptor gene, 37–39 of D5 dopamine receptor gene, 39–40 resensitization, 207–208 D2-like dopamine receptors, 11, 24 D2 dopamine receptor genes regulatory and promoter regions, 28–30 structure and organization, 27–28 D3 dopamine receptor genes regulatory and promoter regions, 31–33 structure and organization, 30–31 D4 dopamine receptor genes regulatory and promoter regions, 34–36 structure and organization, 33–34 desensitization, 202–203 drugs used, for diseases, 101, 102 dopamine receptor agonists and antagonists, 101–103 internalization, 206–207 resensitization, 208–209 D2L receptors, see D2 dopamine receptor D1 /NMDA interaction, in direct GABA pathway, 269–270 Domain swapping, 57 Dopamine agonists Ki values, 102 and L-DOPA comparison between, 556–558 treatment of Parkinson’s disease continuous and pulsatile stimulation, 558–559 DA agonists and L-DOPA comparison between, 556–558 dyskinesia-inducing properties, 555–556 Dopamine (DA), 24, 175–176, 186, 303–304 dysregulation in schizophrenia, see Schizophrenia and glutamate receptor interactions, see Dopamine (DA)–glutamate receptor interactions neurons, 155, 156, 157, 158, 481, 484, 488, 490, 496, 497, 498 phasic and tonic firing pattern, 374 Index publications on, 10 striatal activity and role of, 176–177 D1 receptor, 177–179 D2 receptor, 179–180 See also Dopamine receptors (DARs); Synaptic plasticity in striatum Dopamine (DA)–glutamate receptor interactions, 281–282 in cerebral cortex and striatum, 286 classical model of, 292–293 DA modulation of glutamate receptor-mediated responses, 285–291 glutamate release, 284–285 voltage-gated channels, 283–284 DA receptors subtypes, 282 functional outcome of, 293–294 genetic manipulations of, 291–292 glutamate receptors, 282 in striatum, morphological framework, 282–283 Dopamine precursor levodopa (L-DOPA) treatment and DA agonists comparison between, 556–558 in dyskinetic versus non-dyskinetic animal abnormal involuntary movements (AIMs), 550–551 suppression of, 552 immediate early genes and transcription factors ΔFOSB proteins, 553 Homer-1a isoform, 554 induced elevation, 553–554 supersensitive activation in, 552–553 induced dyskinesia, molecular mechanisms and supersensitivity DA receptor, 560–561 dopaminergic, 561–563 molecular consequences of dopamine depletion chronic L-DOPA treatment, 549–550 MPTP-lesioned monkey, 549 NMDA receptor activation, 550 paradoxical effects of, 554 signaling consequences of dopamine depletion normalized DA null mice, chronic, 547 induced dyskinesia, signaling mechanisms of, 548 Dopamine receptor-interacting proteins (DRIPs), 219–220 637 DAR–DRIP interaction, 226–227 location of, 228–229 model system for study of, 229 verification and significance of, 227 discovery of DAR signalplex bacterial two-hybrid system, 223–224 GST pull-down assay, 224–225 MS-based proteomics, 225–226 protein microarrays, 225 split-ubiquitin system, 223 yeast two-hybrid system, 223 dopamine receptor interacting protein 78 (DRIP78), 197, 231 signalplex, 219–222 See also Dopamine receptors (DARs) signalplex protein members Dopamine receptor knockouts, behavioral findings in, 332–334 D1 /D2 double knockout, 359 D1 /D3 double knockout, 359–360 D2 /D3 double knockout, 360–361 D1 knockouts drug-induced behavior, 329–330 phenotype, interpretation of, 331, 335–336 spontaneous behavior, 327–329 D2 knockouts drug-induced behavior, 342–344 phenotype, interpretation of, 345–348 spontaneous behavior, 340–342 D3 knockouts drug-induced behavior, 350–352 phenotype, interpretation of, 352–355 spontaneous behavior, 348–350 D4 knockouts drug-induced behavior, 356–357 phenotype, interpretation of, 357–359 spontaneous behavior, 355–356 D5 knockouts drug-induced behavior, 337–338 phenotype, interpretation of, 338–340 spontaneous behavior, 336–337 D1-like receptor family, 327 D2-like receptor family, 340 D2L knockouts, 344–345 Dopamine receptor regulating factor (DRRF), 30 and D1 dopamine receptor, 39 Dopamine receptors (DARs), 24, 75–76, 137–138, 195–196, 587–588 ADHD, 588 as antipsychotic receptor, 4–5, 8–9 brain, receptors distribution in, 530–531 638 Dopamine receptors (cont.) colocalization in striatum, 283 coupling to G proteins, 139–140 DAR knockout (KO) mice, 304–306 DARPP-32 phosphorylation, 532–533 dopaminergic activation, 534 D1 /D2 receptor synergism, 153–154 denervation-induced supersensitivity of, 534–535 drugs of abuse, DAR KO mice response to, 315 D1 R KO mice, 311–312 D2 R KO mice, 312–313 D3 R KO mice, 313–314 D4 R KO mice, 314 D5 R KO mice, 314–315 expression, 138–139 findings of, 6–8 function and neuropsychiatric disease cAMP production, inhibition of, 591–592 D1 receptor (DRD1) gene, 591 D2 receptor (DRD2) gene, 595–596, 600 D3 receptor (DRD3) gene, 600–601, 605 D4 receptor (DRD4) gene, 605–606, 614 D5 receptor (DRD5) gene, 614–618 gene organization and transcriptional regulation of, 25–26 genetic deletion, 480 groups of, 11–13, 49 D1 -like dopamine receptor, 24 D2 -like dopamine receptors, 24 heterologous sensitization, 154–155 molecular characteristics of, 588–589 molecular mechanisms arrestin and GRK-mediated desensitization mechanism, 543–544 DA depletion, signaling alterations studies, 545 GPCRs, desensitization process, 543 G protein-coupled receptor (GPCR), 542 G protein-coupled receptor kinase (GRK), arrestin binding, 543 G protein-mediated signaling, 542 RGS9-2 expression regulation, 544 supersensitivity, magnitude, 541 motor behavior, use of KO mice for control of, 306–308, 310 Index D1 R KO mice, 308 D2 R KO mice, 308–309 D3 R KO mice, 309 D4 R KO mice, 309–310 D5 R KO mice, 310 nomenclature of, 5–8 Nurr77 D2 receptors in intact striatum inhibits, tonic stimulation of, 539–540 oligomerization, 256 receptor mosaics (RMs), 258–260, 272 receptor–receptor interactions, 256–258 type RM (RM1), 258–259 type RM (RM2), 259 pharmacological profile of, 590–591 potential glycosylation sites, 589 publications on, 10 receptor signaling, modifications D2 receptor-mediated, changes in, 537–540 proteins, basal activity/expression changes in, 536–537 regulation of behavior by, 323–324 knockout mice, studies on, see Dopamine receptor knockouts, behavioral findings in psychopharmacological studies, 324–327 regulation of ion channels by, 141–142 signaling, 138 adenylate cyclase regulation, 140–142 Akt/GSK-3β pathway, regulation of, 151–153 arrestin-dependent signaling, 146–147 coupling to G proteins, 139–140 cyclic AMP-dependent signaling, 142–143 MAP kinases regulation, 147–151 phospholipase C regulation, 143–146 signaling modifications hemiparkinsonian rat model, 531 6-hydroxydopamine (6-OHDA), 531 releaser amphetamine, 531–532 responsiveness, changes in, 532, 534–535 transcription factors, effects, 535–536 signaling, modifications, 531–540 D1 and D2 receptors, synergism role of, 540–541 in striatum, loss, 526 structural characteristics carboxy-terminus length (C-terminus), 590 Index subtypes, role of, 479–480 transport of, see Dopamine receptor trafficking regulation See also Receptor mosaics types Dopamine receptors (DARs) protein complex, see Signalplex Dopamine receptors (DARs) signalplex protein members, 229 anchoring, scaffolding, and adaptor proteins, 235 arrestin, 238 caveolin-1, 237 filamin-A, 235 H-FABP, 237 MUPP1, 236–237 protein 4.1 N, 235–236 radixin, 236 spinophilin, 236 ion channels and pumps, 243 AMPA receptors, 245 CLIC6, 243 GABA receptors, 246 GIRK, 244 Na+ ,K+ -ATPase, 244–245 NMDA receptor, 245–246 TRPC1, 244 neurotransmitter transporters, 247 DAT, 247 signaling proteins, 238 calcineurin, 240 calmodulin, 240–241 CAPS1, 239 NCS-1, 239 Par-4, 241 protein kinases, 242 PSD-95, 241–242 RGS19, 242–243 S100B, 240 ZIP1, 242 targeting and trafficking proteins, 229–230 AIP1, 231–232 calnexin, 230 DRIP78, 231 dynamin-2, 232–233 GASP, 234–235 GIPC, 233 NF-M, 232 NSF, 233–234 SNX1, 234 Dopamine receptor trafficking regulation biosynthesis and cell-surface trafficking of, 196 calnexin, involvement of, 196–197 639 glycosylation, role of, 198–199 triple phenylalanine motif and DRiP78, 197 desensitization of D1 –D2 heteromers, 203–204 of D1 -like receptors, 200–202 of D2 -like receptors, 202–203 dysregulation in health and disease, 209–210 internalization of D1 –D2 heteromers, 207 of D1 -like receptors, 204–206 of D2 -like receptors, 206–207 resensitization of D1 -like receptors, 207–208 of D2 -like receptors, 208–209 stabilization of receptors at cell surface, 199 NMDA-D1 receptor trap, 199 scaffolding proteins, role of, 200 Dopamine stabilizers, 444 Dopamine transporter (DAT), 247, 403, 408410, 412413 Dăorfler, M., 101124 Dougherty, D D., 410 Downstream heteromer-specific signaling machinery, 57 Doxanthrine (DOX), 85–86 DPAT bioisosteres, 105 heterocyclic, 105–106 non-aromatic, 106–107 D1/PKA cascade, effects of, 177 Drago, J., 336 D1 receptor (DRD1) gene case–control studies, 595 polymorphisms and neuropsychiatric diseases, 593–594 representation, 592 5’ untranslated region (5’ UTR) coding region, 592 D2 receptor (DRD2) gene kinase domain containing (ANKK1) gene, 596 neuroleptics, 600 polymorphisms and neuropsychiatric diseases, 595–599 representation of, 596 STRP, 596 Taq I polymorphisms, allele frequencies, 595 D4 receptor (DRD4) gene coding region, 606 polymorphism 640 D4 receptor (cont.) and neuropsychiatric diseases, 607–613 representation of, 605 and schizophrenia, relationship between, 606, 614 studies, 605–606, 614 48 bp tandem repeat (VNTR) investigation, 605–606, 614 D3 receptors (DRD3) gene bipolar disorder association with Ser9Gly polymorphism, 601, 605 coding region, 600 polymorphism and neuropsychiatric diseases, 602–604 representation of, 601 studies in, 600–601 Dresel, S., 410 D1R-mediated Gq signaling, 55–56 Drug-induced euphoria in humans, D1 -like receptors role in, 485 Drug-seeking behavior mesolimbic dopamine system, 499–500 second-order schedule, 500 Drug self-administration, modulation cocaine injection dose, 492, 495 dopamine receptor subtypes alcohol self-administration, modulation, 498–499 cocaine and amphetamine involvement, 492–494 cocaine, fixed ratio infusion, 495–496 genetic deletion of, 494 intracranial infusion studies, 495 opiate and nicotine self-administration, modulation, 496–497 intranucleus accumbens shell infusions, 493 studies, 491–492 D4 -Selective ligands partial agonists, 115 selective D4 agonists, 114–119 selective D4 antagonists, 119–121 selective D4 radioligands, 122–124 D3 -Selective radioligands D2 /D3 radioligands for PET, 112 subtype-selective, 113 D’Souza, U M., 23–40 Dulawa, S C., 355 Dynamin-2, 232–233 Index Dyskinesias, 209 Dyskinetic animals, 549–551, 553, 556, 560, 561, 562 NR2B subunit, mislocalization importance of, 552 E Ecopipam (SCH 39166), cocaine-induced euphoria in human, 485 Ehringer, H., 8–9 Elliot, E E., 337 Endoplasmic reticulum (ER) quality control system, see Dopamine receptor trafficking regulation Enguehard-Gueiffier, C., 118 Enhanced green fluorescent protein (EGFP), 283 Epidermal growth factor receptor (EGFR), 150 Ergoline CY208-243, 88 Ericksen, S S., 47–60 ERK1/2 pathway, activation of, 147–150 Eticlopride D2 -like agonist and cocaine self administration, 493 Extracellular loop 2(ECL2), 52–54 Extracellular-regulated kinases (ERKs), 147, 148 Extrapyramidal motor symptoms (EPS), 209, 436 F Fananserin, 453 FAUC 179, 117 FAUC 213, 119–120 FAUC 365, 113 FAUC 2020, 119 Faure, M., 149 Faure, V., 149 Filamin A., 200, 235, 265 Five choice serial reaction time task (5CSRTT), 377, 381 Floresco, S B., 380, 384 Fluorescence resonance energy transfer (FRET) microscopy, 262 Fowler, J S., 414 Frankie, H F., 585–619 Frank, M J., 385, 387 Freeman, H S., 87 Free, R B., 219–248 Freyberg, Z., 47–60 Friedman, E., 145 Fukunaga, K., 237 Fuxe, K., 255–273 Index G GAIP-interacting protein C terminus (GIPC), 233 γ-Aminobutyric acid GABAergic transmission, 539 receptors, 246 Gelernter, J., 600 George, S R., 193–211 Ginovart, N., 431–457 Giorgi, O., 375 Gjedde, A., 409 Glatt, S J., 14, 614 Glial-derived neurotrophic factor (GDNF), 567 Glutamate receptors, 434–435 ionotropic receptors, 282 metabotropic receptors, 282 Glutamatergic synaptic transmission long-term depression of, 180–181 long-term potentiation of, 181 Glutathione (GSH), 224 Glutathione-S-transferase (GST), 224 Glycogen synthase kinase (GSK3), 151, 238 Gmeiner, P., 101–124 Goldman, D., 600 GPCR-associated sorting protein (GASP), 208 G protein, 139 coupling of dopamine receptor subtypes to, 139–140 heterotrimer, 139 G protein-activated inwardly rectifying potassium channels (GIRKs), 244 G protein-coupled receptor-associated sorting protein (GASP), 234–235 G protein-coupled receptors (GPCRs), 47–49, 542 activation mechanism, 50 ionic lock, role of, 50 molecular switches in, 50 arrestin binding, continuous stimulation via GRK-mediated phosphorylation, 556 binding sites, 50–52 classes of, 48 extracellular loop (ECL2), 52–54 oligomerization, 54–55 consequences of, 60 dimer interface, 57–58 and GPCR–G protein interactions, 59–60 rearrangement upon receptor activation, 58–59 and signaling, 55–57 structure of, 48 641 trafficking as oligomer, 194–195 transmembrane (TM) segment interactions, 49–50 G-protein receptor kinases (GRKs), 194 and D1 receptor desensitization, 201 and D2 receptor desensitization, 202 role in D1 receptor internalization, 204–205 G protein-regulated inwardly rectifying potassium (GIRK), 156–158 Gq-mediated signaling, 55 Gq/11 pathway in D1 /D2 RM1, 261 Granon, S., 381 Gratton, A., 376 Grunder, G., 404 Guidolin, D., 255–273 Guo, N., 55, 57 Guo, W., 55, 57 Guo, Y., 55, 57 Gurevich, E V., 525–568 Gurevich, V V., 525–568 H Haloperidol, 306 for antipsychotic receptor identification, 4–6 Hamadani, K Jr., 260 Hazelwood, L A., 219–248 Heart-type fatty acid binding protein (H-FABP), 237 Heroin drug dopamine receptor subtypes modulation of, 506–507 treatment in, 496–497 Heydorn, A., 208 Heykants, J J P Dr., 4–5 Hirvonen, J., 13 Holmes, A., 337 Holmes, D., 303–316 Hornykiewicz, O., 8–9 Human β2 adrenergic receptor (B2AR), 48 I Iitaka, C., 303–316 Immediate early gene (IEG), 535 Inositol trisphosphate (IP3), 143 Inverted-U dose–response function theory, and PFC DA signaling, 380–382 in vivo imaging, of dopaminergic receptors, 399–400 and ADHD, 410 in affective disorders bipolar disorder, 408–409 major depressive disorder, 408 642 in vivo imaging (cont.) and drugs of abuse, 410–411 alcohol, 415–416 cocaine, 411–413 methamphetamine, 413–414 nicotine, 414–415 personality disorders and traits, 409–410 in schizophrenia, 400–401 antipsychotic drug occupancy studies, 406–408 extrastriatal D2 receptors, 405–406 prefrontal DA receptors, 406 striatal DA transmission and receptors, 401–405 social phobia and, 409 Ionic lock, 50 J Janssen, P A J Dr., Jastrzebska, B., 59 Javitch, J A., 4760 Jocoy, E L., 281295 Jăonsson, E G., 14 K Kapur, S., 431–457 Katz, J L., 357 Kelley, A E., 488 Kestler, L P., 401 Ketamine, 435 Khan, Z U., 138 Kim, D., 150 Kinase domain containing (ANKK1) gene, 596 Klco, J M., 53–54 Kleinau, G., 54 Knockout (KO) technology, 304–305 See also Dopamine receptor knockouts, behavioral findings in; Dopamine receptors (DARs) Koshikawa, N., 323–361 Koshland, D E., 260 Kreitzer, A C., 180 L Large dense-core vesicles (LDCV), 239 Laruelle, M., 399–418 L-DOPA-induced dyskinesia (LID), 261, 558 neural mechanisms of, 546 NMDA receptor-mediated transmission, abnormalities in, 552 striatal circuit, 546–547 studies of, 562–563 Lee, F H F., 585–619 Index Lee, M S., 602 Leriche, L., 351, 354 Leukotriene B4 (LTB4 ) receptor, 58 Levine, M S., 281–295 Liang, K Y., 57 Liang, Y., 57 Lieberman, J A., 14 Lindqvist, M., 9–10, 433, 439 Lister-hooded rat, 485 Lithium, 151 Liu, F Dr., 269, 271 Liu, Q., 595 Liu, X., 595 Lăober, S., 118119 LongEvans rats, 486 Long-term depression (LTD), 180–181 Luo, Y Q., 149 M Malenka, R C., 180 Malison, R T., 412 Marcellino, D., 255–273 Marshall, J F., 154 Martinez, D., 412 Mass spectroscopy (MS), 224, 225 Matulenko, M A., 114, 122 McDermed, J D., 79, 106 Medium spiny neurons (MSNs), 176, 283 dopamine effects on, 307 D1 receptor-signaling pathway in, 177–179 D2 receptor-signaling pathway in, 179–180 Mehta, M A., 384, 386 Mesolimbic dopamine system, pre- and post-synaptic receptors in, 480, 499–500 Methamphetamine abusers, imaging studies on, 413–414 2-Methyldihydrexidine, 81–82 Methylphenidate, 410 1-Methyl 4-phenyl 1,2,3,4-tetrahydropyridine (MPTP) induced Parkinsonian symptoms, 81 lesioned marmoset model of Parkinson’s disease, 84 striatum treatment, 531 N -Methylspiperone (MSP), dopamine D2 receptor docking, 51 MGlu receptor heteromers, 59 Mill, J., 606, 607 Misener, V L., 595 Mitogen-activated protein kinase phosphatase (MKP) inhibition of, 539 Index Mitogen-activated protein (MAP) kinases, 147–148 D1-like receptors regulation of, 148–149 D2-like receptors regulation of, 149–151 Mitogenesis, 106, 114, 117, 118, 119, 124, 148, 150 D2-like receptors activation and, 150 M3 muscarinic acetylcholine receptor (M3R), 54 Moghaddam, B., 377 Molecular switches, 50 Monoamine oxidase (MAO), 558 Monohydroxylated dipropylaminotetralins (DPATs), 104 Montgomery, A J., 414 Moreira, I S., 47–60 Multi-PDZ-domain-containing protein (MUPP1), 236–237 N Nafadotride, 102 Nakane, M., 121 Negash, K., 89 Nemonapride, 102 Neocortical dopamine receptors modulation, cocaine-seeking behavior, 505 N -Ethylmaleimide-sensitive factor (NSF), 233–234 Neurodegenerative diseases, role of DA–NMDA interactions in, 293–294 Neurofilament-M (NF-M), 232 Neurokinin (NK3 ) receptors, in schizophrenia treatment, 456–457 Neuronal calcium sensor-1 (NCS-1), 239 Neuropsychiatric disease, 585, 586, 589–618 symptoms and functional impairments in, 588 Neurotensin (NT), 263 Neve, K A., 137–159 Nichols, D E., 75–97 Nicotine drug, 496–497 dopamine receptor subtypes modulation of, 506–507 self-administration in, 497 smokers, DA system in, 414–415 N -methyl-D-aspartate (NMDA) receptors, 245–246, 282, 288–289, 293–294 and DA receptors, 288–291 glutamate receptor antagonist, 488 hypofunction in schizophrenia, 435 LID mediated transmission, abnormalities in, 552 643 redistribution, between, 552 See also Schizophrenia Nomifensine, 79–80 Noncatechol ergoline partial D1 agonist CY208-243, 88 N-terminal Venus flytrap (VTF) module, 54–55 NT receptor subtype (NTS1), 263 O O’Dowd, B F., 193–211 Opiate reward, 496–497 Oral nicotine self-administration, 497 O’Reilly, R C., 385, 387 O’Sullivan, G J., 323–361 O’Tuathaigh, C., 323–361 P Parello, J., 59 Parkinson’s disease (PD), 81, 281, 294 Akt-GSK3 pathway, 561 Akt pathway, 567 apomorphine in, 77 DA–glutamate receptor interactions and, 294 dopamine agonists (DA), treatment in continuous versus pulsatile stimulation of, 558–559 DA Agonists and L-DOPA comparison between, 556–558 dyskinesia-inducing properties, 555–556 dopamine (DA) in parkinsonian brain, loss, 542 in striatum, loss, 526 dopamine receptor expression, changes, 530 D2 receptor increases in striatum, 530–531 1-methyl 4-phenyl 1,2,3,4tetrahydropyridine (MPTP), treatment, 531 dopamine receptor, molecular mechanisms G protein-coupled receptor (GPCR), 542 supersensitivity, magnitude, 541 dopamine receptors and neuroprotection in DA replacement therapy, effect, 566–567 tyrosine hydroxylase (TH), proportion, 566 dopamine receptor signaling, modifications D1 and D2 receptors, role of, 540–541 D2 receptor-mediated, changes in, 537–540 644 Parkinson’s (cont.) hemiparkinsonian rat model, 531 6-hydroxydopamine (6-OHDA), 531 proteins, basal activity/expression changes in, 536–537 responsiveness, changes in, 532, 534–535 transcription factors, effects, 535–536 forebrain of rodents and primates, DA receptors in alterations, illustrations of, 528 cyclic adenosine monophosphate (cAMP), accumulation of, 527–528 D3 receptor, pharmacological properties of, 530 in situ hybridization labeling studies, 527–528 striatal output neurons in, 527 Gαolf and Gγ 7, concentration of, 530 hemiparkinsonian rat model of, 534 homologous desensitization system, 556–557 L-DOPA-induced dyskinesia, molecular mechanisms critical elements in, 559–560 DA receptor supersensitivity and, 560–561 dopaminergic supersensitivity, 561–563 L-DOPA-induced motor fluctuations, mechanisms, 564, 566 L-DOPA treatment, effects dopamine depletion normalized, 547 dopamine depletion unchanged, 549–550 in dyskinetic versus non-dyskinetic animal, 550–552 immediate early genes and transcription factors, 552–554 induced dyskinesia, signaling mechanisms, 548 L-DOPA treatment, result of, 526–527 motor symptoms, DA receptors and treatment L-DOPA-induced dyskinesia, replacement therapy and pathophysiology, 545–547 MPTP monkey model, 534–535 Patil, S T., 455 Pato, C N., 596 Index Pato, M T., 597 Pavlovian learning processes, 487 PD-168077, 114–115 Penny, J B., 176 Pergolide, 101 Perreault, M L., 193–211 Personality disorders (PD), 409 Phencyclidine (PCP), 435 1-Phenyl-3-benzazepines, 77 D1 affinity, 79 D1 -selective ligands, 78 gauche conformation, 78 Phenylpiperazines, 109 aromatic residues of type π 2, 109 binding affinities, 111 linker units, 110 variations at π 1, 110–111 4-Phenyltetrahydroisoquinolines, 79–80 Phillips, P E., 376, 380 Phosphatidylinositol-3 kinase (PI-3K), 151 Phospholipase C (PLC), 143 D1-like receptor regulation of, 143–144 D2-like receptor regulation of, 144 regulation by D1 and D2 receptor heteromers, 145–146 signaling, behavioral implications of, 146 Pilowsky, L S., 407 PKA-deficient mice, 143 Platelet-derived growth factor receptor (PDGFR), 144 Polymerase chain reaction (PCR) methods, 592 Positron emission tomography (PET), 112, 399–400 Post-synaptic density 95 (PSD-95), 241–242 PP1 inhibition, 140 Pramipexole, 101 Prante, O., 101–124 Prefrontal cortex (PFC) DA system, 373–374 cognitive function DA role in improving working memory, 382–383 working memory, DA modulation of, 380–382 DA modulation of response flexibility D2 receptors and response flexibility, 384–387 regulation of response flexibility, 387–388 DA receptors in PFC, 378–379 DA release, basic anatomy of, 374 mesocortical DA system, behavioral activation of Index appetitive events, 376 aversive events, 375–376 cognitive processing, 376–377 DA release, 377–378 response to stress, 379–380 role for DA in attentional processing per se, 383–384 Prostate apoptosis response (Par-4), 241 Protein kinase A (PKA), 140, 177 inhibitor post-trial infusion of, 488 role in D1 receptor desensitization, 201 Protein kinase C (PKC), 203 Protein kinase C-ζ-interacting protein (ZIP1), 242 Protein microarrays, 225 Protein 4.1 N, 200, 235–236 Protein phosphatase 2B (calcineurin), 143 Protein phosphatase (PP1), 140, 236 Psychosis and D2 High receptors, 14–15 Q Quinpirole drug, 142, 491, 498 intranucleus accumbens shell infusions of, 504 quinelorane and, 101 treatment, 489–490 R Raclopride D2-like antagonist, 102 and water intake, 487 Radixin, 236 Ramos, M., 303–316 Rashid, A J., 146 Receptor mosaics types DA type receptor mosaics, 260 D1 /D2 heteromer, 260–261 D1 /D3 heteromer, 261 D2 /D3 heteromer, 260 DA type receptor mosaics A2A /D2 heteromer, 264–265 A2A /D3 heteromer, 267 CB1 /D2 heteromer and A2A /D2 /CB RMs, 267–268 D5 /GABA-A RM, 271 A1 /D1 heteromer, 268 D1 /NMDA RM, 269–270 D2 /NMDA RM, 270–271 D2 -non-α7 nAChR heteromer, 264 D2 /RTK type RM, 271 mGluR5/A2A /D2 heteromer, 265–267 μ-opioid receptor/D1 heteromer, 269 putative neuropeptide receptor/D2 heteromers, 262–263 645 somatostatin SSTR5/D2 receptor heteromer, 262 Receptor stimulation tolerance, 556 Receptor tyrosine kinases (RTK), 271 Regulator of G protein signaling 19 (RGS19), 242–243 Relapse process drug-seeking behavior and alcohol, modulation, 506–507 cocaine modulation, 499–500 extinction/reinstatement paradigm, 500 heroin and nicotine, modulation, 506–507 intracranial administration, 503, 505 systemic administration, 501, 503 Restriction fragment length polymorphisms (RFLP), 592 Reverse transcription polymerase chain reaction (RT-PCR), 30 Reward processes D1 -like and D2 -like receptor agonists conditioned place preference with, 485–486 primary mediation, 481 self-administration of, 482–485 natural and endogenous, modulation of alcohol self-administration, 498–499 brain stimulation, 488–490 food and water, 486–487 microinfusions of, 488 opiate and nicotine self-administration, 496–497 pretreatment with, 486–487 psychostimulant self-administration, 492–496 quinpirole, administration of, 485 sexual behavior, 487 sucrose-sham feeding, 487 self-administration apomorphine, 482 intracranial studies, 484 intravenous injections, 482–483 Rhodopsin and oligomerization, 55 Richardson, N R., 376 Richfield, E K., 11, 378 Risperidone, 102 Robbins, T W., 373–389, 490 Romanelli, R J., 137–159 Romanides, A J., 380 Ropinirole, 101 Rotamer toggle switch, 50 Rotigotine, 101 Rubinstein, M., 355, 357 646 S Sahu, A., 146 SB-277011A D3 antagonist and nicotineprimed reinstatement, 506 SCH 23390 D1 -like antagonist, 487 intranucleus accumbens shell infusions of, 493 Schizophrenia, 432 ADHD, 588 antipsychotic drugs atypical antipsychotics, 436–437 neuropharmacology of, 437–438 typical antipsychotics, 435–436 in vitro receptor-binding profile of, 438 DA and glutamatergic systems, interactions between, 435 DA receptors, in antipsychotic drug action, 438–439 antagonist vs inverse agonist, 450–451 D1 receptor blockade, 445–446 D2 receptor blockade, 439–443 D3 receptor blockade, 446–447 D4 receptor blockade, 447 D2 receptor partial agonists, 443–445 fast dissociation and transient D2 occupancy, 451–452 limbic D2 receptor blockade, 452 relapse on withdrawal and supersensitivity, 448–450 speed of onset and implications for mechanism, 447–448 D2 blockade, as mechanism of antipsychotics action, 439 D2 blockade effects, as mechanism of antipsychotics action on catalepsy, 441–442 on c-fos expression, 442 on conditioned avoidance response (CAR), 441 on direct DA agonist-induced behavior, 440–441 on indirect DA agonist-induced behavior, 440 preclinical evidence of, 439–440 in vitro evidence of, 439 density of D2 receptors in, 11–12 High D2 mechanism, 13–14 dopamine hypothesis of, 9–11, 432–434 European case–control studies, 600 glutamate hypothesis of, 434–435 other receptors, in antipsychotic drug action Index α1 and α2 adrenergic receptors blockade, 456 CB1 receptor blockade, 455–456 drugs acting on glutamate system, 454–455 5HT1A receptor activation, 454 5HT2A receptor blockade, 453–454 NK3 receptor blockade, 456–457 WCST, 595 See also Clozapine Schultz, W., 481 Seamans, J K., 373–389 Seeman, P., 1–16, 122 Self, D W., 479–510 Senogles, S E., 59 Ser9 Gly and schizophrenia, 601 relationship, meta-analysis of, 601 Serotonin (5-HT) receptors, 453 in schizophrenia treatment, 453–454 studies, 53–54 Serretti, A., 600 Servan-Schreiber, D., 383 Shen, W., 175–186 Shi, L., 47–60 Short tandem repeat polymorphism (STRP), 596 Sibley, D R., 219–248 Signalplex, 219–221 constituents of, 221 goal of, 222 interaction regions for DRIPs, 221–222 Signal-to-noise ratio, and DA receptor, 382–383 Simpson, M M., 52 Single photon emission computed tomography (SPECT), 399–400 SKF 82958 and SKF 81297, D1 -like agonists, 482 copulation and, 487 intravenous cocaine and, 502 self-administration in drug-naive rats, 483 Snyder, S Dr., Snyder, S E., 89 Snyder, S H., 5–6 Sobell, J L., 617 Somatostatin receptor, 56 Sorting nexin-1 (SNX1), 208, 234 Spencer, T J., 410 Spike-timing-dependent plasticity (STDP), 182 Spinophilin, 236 Spiperone, 102 Split-ubiquitin system, 223 Sprague Dawley rats, 486 Index Squid rhodopsin electron cryomicroscopy (ECM) model, 58 Stefani, M R., 377 Strange, P G., 259 Striatal DA transmission in schizophrenia, studies on, 401 aromatic amino acid decarboxylase activity, 404–405 baseline occupancy of D2 receptors by DA, 404 dopamine receptors, 401–403 dopamine transporter, 403 striatal amphetamine-induced DA release, 403 vesicular monoamine transporter, 403 Striatum cAMP, accumulation of, 532 D2 receptors increases in, 530–531 1-methyl 4-phenyl 1,2,3,4tetrahydropyridine (MPTP), treatment, 530–531 neurodegeneration, 148 striosome–matrix organization, 554 Substituted cysteine accessibility method (SCAM) studies, 49 Sucrose-sham feeding and D1 -like agonists, 487 Sulpiride, 102 Surmeier, D J., 175–186 Synaptic plasticity in striatum dopaminergic modulation of, 181–186 D1 receptor signaling in striatonigral MSNs, 184–186 D2 receptor signaling in striatopallidal MSNs, 182–184 Hebbian synaptic plasticity, induction of, 182 See also Dopamine (DA); Long-term depression (LTD); Long-term potentiation (LTP) T Takeuchi, Y., 237 Tardive dyskinesia (TD), 436 Taylor, J R., 490 Taylor, S F., 403 Thioxanthenes, 102 Thyroid-stimulating hormone receptor (TSHR), 54 Tirotta, E., 303–316 Toggle switch, 50 647 Tomiyama, K., 323–361 Torvinen, M., 267 Transient receptor potential channel (TRPC1), 244 Transmembrane (TM) proteins, 47–48 Transmission disequilibrium tests (TDT), 595 Tunicamycin, and D1 receptor trafficking, 198 Two-photon laser scanning microscopy (2PLSM), 176, 178 Tyrosine hydroxylase, 157 U U-101387, 120–121 V Valjent, E., 147, 148 van der Meulen, E M., 377 van der Meulen, J A., 377 Van Rossum, J M., V1a vasopressin receptor, 53 Verma, V., 193–211 Volkow, N D., 411, 412 W Waddington, J L., 323–361 Wang, Y., 154 Weinberger, D R., 382 Weinstein, H., 47–60 Winand, M., Winterer, G., 382 Wisconsin Card Sorting Test (WCST), 595 Wlliams, J T., 137–159 Wong, A H C., 585–619 Wong, D F., 409 Wong, V., 587–621 Woods, A., 255–273 Woods, A Dr., 270, 271 Wu, J C., 412 X Xu, M., 349–351, 353 Y Yan, Z., 144 Yeast two-hybrid system, 223 Young, A B., 176 Z Zhang, J., 327 Zhao, M M., 53 ... Sanders-Bush, 1988 The Alpha-2 Adrenergic Receptors, EDITED BY Lee Limbird, 1988 The Opiate Receptors, EDITED BY Gavril W Pasternak, 1988 Kim A Neve Editor The Dopamine Receptors Editor Kim A Neve Portland... Discovery, EDITED BY Kim A Neve, 2009 The Cannabinoid Receptors, EDITED BY Patricia H Reggio, 2009 The Glutamate Receptors, Swanson, 2008 EDITED BY Robert W Gereau, IV, and Geoffrey T The Chemokine Receptors, .. .The Dopamine Receptors T HE R ECEPTORS KIM A NEVE, SERIES EDITOR The Dopamine Receptors, Second Edition, EDITED BY Kim A Neve, 2010 Functional Selectivity of G Protein-Coupled Receptor