5

THE INTERNATIONALNARCOTICSRESEARCH CONFERENCE(INRC) '89 / •

Proceedings of a Conference Held at Ste-Adele, Quebec, Canada,July 9- 14, 1989

Editors

Remi QuirionDepartment of Psychiatry

Douglas Hospital Research CentreMcGill University

Verdun, Quebec, Canada

Khem JhamandasDepartment of Pharmacology

Queen's UniversityKingston, Ontario, Canada

Christina GianoulakisDepartment of Psychiatry

Douglas Hospital Research CentreMcGill University

Verdun, Quebec, Canada

ALAN R. LISS, INC. • NEW YORK

Contents

Preface

R. Quirion, C. Gianoulakis, K. Jhamandas xix

Acknowledgments xxi

A Potent and Long-Lasting Ligand: Azabicyclononane (P-7521)Chi Zhiqiang and Jin Wenqiao 1Endogenously Released Opioids Inhibit Inhibitory Post-SynapticPotentials in Guinea Pig CA3 Pyramidal Cells and Rat DentateGranule CellsRobert M. Caudle, Elizabeth Swearengen, and Charles Chavkin 5

Evidence for Four Opioid-Kappa Binding Sites in Guinea Pig BrainRichard B. Rothman, Victor Bykov, Brian R. de Costa, Arthur E. Jacobson,Kenner C. Rice, and Linda S. Brady 9

Dextromethorphan Sites, Sigma Receptors, and the PsychotomimeticEffects of Sigma OpiatesJose M. Musacchio, Martine Klein, and Peter D. Canoll 13

Lack of Evidence for In Vivo Interaction of Steroids WithHaloperidol-Sensitive Sigma (o-H) Binding Sites in Brain and SpleenSiegfried Schwarz and Peter Pohl ':, 17

Investigation of the Mechanism by Which Sigma Ligands InhibitStimulation of Phosphoinositide Metabolism by MuscarinicCholinergic AgonistsWayne D. Bowen, Paul Tolentino, and Paul Varghese 21

Coupling of Mu-Opioid Receptors With Adenylate Cyclase in Naive andMorphine-Tolerant RabbitsJ. Polastron, M.J. Boyer, J.P. Thouvenot, J.C. Meunier, and Ph. Jauzac 25

Binding Sites for Non-Opioid 7-Type Endorphins in Brain Structuresof the Mesocorticolimbic Feedback CircuitVictor M. Wiegant, Eric Ronken, Thijs de Boer, and Jeroen A.D.M. Tonnaer . . 29

The Novel Antagonist Profile of (-)MetazocineIlona Berzetei-Gurske and Gilda H. Loew 33

Vll

viii / Contents

Cyprodime Analogs: Synthesis and Pharmacological EvaluationHelmut Schmidhammer, Colin F.C. Smith, Daniela Erlach, Martin Koch,Roland Krassnig, Wolfgang Schwetz, and Christine Wechner 37

5-Methylated Naloxone, Naltrexone, Oxymorphone, and Their14-O-Methyl EthersHelmut Schmidhammer, J. David Leander, Karin Mayer-Valkanover,Christine Nussbaumer, Christine Schmidt, Darryle D. Schoepp,Andrea Schratz, and Michaela Walla-Kugler 41

N,N-Diallylated Analogs of Dynorphin A-(l-13) as Potent Antagonistsfor the Endogenous Peptide and Selective K-Opioid AnalgesicsSimon Lemaire, Paul Parent, Chantal Lapierre, and Robert Michelot 45

In Vivo Opioid Activity of S-Methyl and S-Allyl Morphinan DerivativesFrancois B. Jolicoeur, Daniel Menard, Bernard Belleau, and Simon Lemaire . . . 49

Peripheral Antinociceptive Effect of an Extremely ^-Selective PolarDermorphin Analog (DALDA)Peter W. Schiller, Thi M.-D. Nguyen, Nga N. Chung, Gervais Dionne,and Rene Martel ' 53

Kinetic Studies on Binding of [3H]B-Funaltrexamine ([3H]B-FNA) toMu Opioid ReceptorsLee-Yuan Liu-Chen, S. Li, O. Holowecky, and R.J. Tallarida 57

[9H]B-Funaltrexamine ([3H]B-FNA) Binds Irreversibly to Mu OpioidReceptors in the Rat Brain: Autoradiographic StudyLee-Yuan Liu-Chen, Shuixing Li, Kenneth W. Rohrbach,and Michael E. Lewis 61

Nor-Binaltorphimine is a Reversible, Noncompetitive Opioid Antagonistin the Mouse Vas Deferens With High Affinity for Kappa Receptors inMonkey Brain MembranesC.B. Smith, F. Medzihradsky, P.J. Hollingsworth, B. de Costa, K.C. Rice,and J.H. Woods 65

Isolation of Kappa-Opioid Receptor With an Aminoethyl-Nor-Binaltorphimine (AE-norBNI) Affinity ColumnZ.H. Song, D.P. Barbas, P.S. Portoghese, and A.E. Takemori 69

Selectivity Profile of Nor-Binaltorphimine and ICI-197,067 in GuineaPig BrainJacques Magnan aria Mario Tiberi 73

The Affinity Ligand "UPHIT" Acylates Kappa-Opioid Binding Sites In VivoL . B a n d , B . R . d e C o s t a , V . B y k o v , A . Per t , K . C . R i c e , and R . B . R o t h m a n . . . 7 7

Inhibition of Cholinergic Analgesia by (+ )-OpiatesJ. Michael Walker, Saundra L. Patrick, Andrew Thurkauf, Kenner C. Rice,and Wayne D. Bowen 81

Selectivity of Some "Specific" Opioid Ligands?Elena Fiorica-Howells and Sydney Spector 85

Contents / ix

Inactivation of Kappa Opioid Receptors by N-EthylmaleimideAnna Borsodi, Jolanta Zawilska, and Abel Lajtha 89

Canine Brain Radioreceptor Assay for Non-Specific Opioid PeptideScreening in Dog Heart ExtractsBarbara A. Barron and James L. Caffrey 93

Purification of Solubilized Opioid Binding Sites From Rat Brain byPhotoaffinity Labeling and Affinity Chromatography Using Specific8-Opioid Antagonist Exorphin AnalogsSpyros Loukas, Fotis Panetsos, and Christine Zioudrou 97

Non-Peptide Photoaffinity Probes of the jt-Opioid ReceptorAnnick Mejean, Maurice Goeldner, and Christian Hirth 101

Cross-Linking of l25I-Beta-Endorphin to Rat Striatal Mu- and Delta-Opioid Receptors Under Physiological Conditions: Evidence for anOpioid Receptor ComplexAnton N.M. Schoffelmeer, Yi-He Yao, and Eric J. Simon 105

Effects of Calcium-Channel Blockers (CCB) on |i- and 8-Opioid Receptorsin Rat Brain MembranesSiegfried Schwarz and Aspandiar G. Katki 109

Differential Inhibition of Delta-Opiate Binding and Low-Km GTPaseStimulation by Phospholipase A2 TreatmentDan F. Lazar and Fedor Medzihradsky 113

Characterization of [3H] (+ )-Pentazocine, a Highly SelectiveSigma LigandWayne D. Bowen, Brian de Costa, Susan B. Hellewell, Andrew Thurkauf,J. Michael Walker, and Kenner C. Rice 117

Characterization of Opioid Binding Sites Using Selective AntagonistsAndrew J. Lawrence and John R. Traynor 121

Down-Regulation of Sigma Receptors by Chronic HaloperidolRae R. Matsumoto, Wayne D. Bowen, and J. Michael Walker 125

The Effect of Sigma Ligands on Dextromethorphan Binding Sites in theGuinea PigMartine Klein, Guangzhao Zhou, John J. Paturzo and Jos6 Musacchio 129

Characterization of (+ )-[3H]3-PPP and [3H]TCP Binding Sites inMembrane Preparations of Bovine Adrenal MedullaC.A. Rogers and S. Lemaire 133

Morphine Induces an Intracellular Alkalinization in Bovine AorticEndothelial Cells (BAECs)Juliann G. Kiang and M. Colden-Stanfield 137

Developmental Pattern of Opioid Receptors in the Striatum andHippocampus: Evidence for a Non-Mature Type of Receptor inEmbryonic TissueJacob Barg, Victor Hatini, and Rabi Simantov 141

x / Contents

Binding Characteristics of Opioid Ligands to Receptors ReconstitutedInto Several Types of LiposomesM. Maruyama 145

Substance P Modulation of [3H]DAGO Binding in the Brain ofSwiss-Webster and CXBK (Mu-Opioid Receptor-Deficient) MiceS.A. Krumins, D.C. Kim, and A.A. Larson 149

Effect of Repeated Administration of U-50,488H on the Binding of3H-SCH 23390 and 3H-Spiperone to Rat Brain and Spinal CordDopamine ReceptorsHemendra N. Bhargava, Poduri Ramarao, and Anil Gulati 153

Effects of Up-Regulation by Butyrate on 8-Opioid Receptor GTPSensitivity and Distribution in Subcellular CompartmentsCarmine J. Coscia, Mariana Belcheva, Xiao-Ming Gao, and De-Maw Chuang . . 157

Localization, Properties, and Subtypes of Opioid Receptors inCanine Small IntestineSultan Ahmad, H.D. Allescher, Peter Kostka, C.Y. Kwan, andEdwin E. Daniel 161

Autoradiographic Demonstration of [3H]Loperamide Binding to OpioidReceptors in Rat and Human Small IntestineM.R. Dashwood, R.M. Sykes, and C.S. Thomson 165

Autoradiographic Localization of [3H]Dextromethorphan (DM) in GuineaPig Brain: Allosteric Enhancement by RopizinePeter D. Canoll, P. Ross Smith, Suzy Gottesman, and Jos6 M. Musacchio 171

Modulation of Mu-Opioid Binding Sites in Rat Spinal Cord by ChronicIntrathecal Infusion of Morphine and Naloxone: A QuantitativeAutoradiography ApproachChristine Gouarderes, Khem Jhamandas, Jean-Marie Zajac, Alain Beaudet,Jean Cros, and Remi Quirion 175

The Use of [3H]DAGO to Label Projections of Thin Primary AfferentFibers at the Superficial Dorsal Horn Level of the Rat Spinal CordDominique Besse, Marie-Christine Lombard, Jean-Marie Zajac,Bernard P. Roques, and Jean-Marie Besson 179

Pre- and Postsynaptic Location of Mu-, Delta-, and Kappa-OpioidReceptors in the Superficial Layers of the Dorsal Horn of the Rat Spinal CordDominique Besse, Marie-Christine Lombard, Jean-Marie Zajac,Bernard P. Roques, and Jean-Marie Besson 183

Stimulus-Induced Feeding Alters Regional Opiate Receptor Bindingin the Rat: An In Vivo Audioradiographic StudyElliot A. Stein, Kenneth D. Carr, and Eric J. Simon 187

Release of Dynorphin A in Cat Spinal Cord In VivoWilliam D. Hutchison and Cecil R. Morton 191

Contents / xi

Tyrosine Hydroxylase and Enkephalin in the Rostral VentrolateralMedulla: Major Synaptic Contacts From Opioid Terminals onCatecholaminergic NeuronsTeresa A. Milner, Virginia M. Pickel, and Donald J. Reis 195

Localization of Neutral Endopeptidase-24.11 (Enkephalinase) toN-Methyl-D-Aspartate-Sensitive Cell Populations in the Rat ForebrainStephen A. Back and Charles Gorenstein 199

Adaptative Changes in Two Indices of Enkephalin Neuron Activity inMouse Striatum Following Gabaergic StimulationCatherine Llorens-Cortes, Bruno Giros, Tam T. Quach, andJean-Charles Schwartz 203

Effect of Hypophysectomy on Dynorphin mRNA and Peptide Contentin the Rat Adrenal GlandRobert Day, Martin K.-H. Schafer, Stanley J. Watson, and Huda Akil 207

Prodynorphin Messenger RNA Expression in the Rat Anterior Pituitaryis Regulated by EstrogenSanti Spampinato, Tiziana Bachetti, Marco Canossa, and Sergio Ferri ...- 211

Morphine Increases Proenkephalin Gene Expression in the AdrenalMedulla by a Central MechanismSusanne Reimer and Volker Hollt 215

Effects of Electrical Stimulation in the Periaqueductal Gray on POMCPeptides and mRNA in the Rat BrainDavid Bronstein and Huda Akil 219

Pharmacological Regulation of Striatal Prodynorphin PeptidesKeith A. Trujillo and Huda Akil 223

The Effects of Nigrostriatal 6-Hydroxydopamine Lesions on Dopamine D2

Receptor mRNA and Opioid SystemsA. Mansour, J.H. Meador-Woodruff, D.M. Camp, T.E. Robinson, J. Bunzow,H. Van Tol, O. Civelli, H. Akil, and S.J. Watson 227

Identification of Prodynorphin and Proenkephalin mRNA-ExpressingCells in the Neurointermediate Lobe of the Rat Pituitary GlandMartin K.-H. Schafer, Robert Day, Huda Akil, and Stanley J. Watson 231

Opioid Peptide mRNAs in the Rat PinealVincent J. Aloyo, Michael E. Lewis, and Richard F. Walker 235

Proenkephalin Gene Expression in Cultured Chromaffin Cells isRegulated at the Transcriptional LevelC.J. Farin, V. Hollt, and N. Kley 239

Adrenal Dynorphin A and Leu-Enkephalin Levels in NormotensiveWistar Kyoto (WKY) and Spontaneously Hypertensive Rats (SHR)Michel Dumont, Luc Sabourin, and Simon Lemaire 243

Characterization of a Dynorphin-Converting Enzyme in theBovine PituitaryLakshmi Devi 247

xii / Contents

HPLC-ECD Determination of the Enzymatic Hydrolysis of [LEU]- and[METJEnkephalin in Rat PlasmaShinji Shibanoki, Susan B. Weinberger, Koichi Ishikawa,and Joe L. Martinez, Jr 253

The Release of a-Neoendorphin From Rat Hippocampus Following KainicAcid-Induced SeizuresWfadys/aw Lasori, Barbara Przew/ocka, and Ryszard Przew/ocki 257

Conversion of the Dynorphins to Leu-Enkephalin in HumanSpinal CordFred Nyberg and Jerzy Silberring 261

Tyrosine Hydroxylase and Enkephalin in Nuclei of the Solitary Tracts:Co-Existence and Convergent Synaptic Input to Catecholamine NeuronsVirginia M. Pickel, June Chan, and Teresa A. Milner 267

Is Cathepsin B an Enkephalin-Processing Enzyme in the Tooth Pulp?T. Kudo, E.-Q. Wei, and R. Inoki 271

Characteristics of BANA-Degrading Enzyme in the Tooth PulpActivated by BradykininT. Kudo, E.-Q. Wei, and R. Inoki 275

The Effects of Morphine on Norepinephrine-StimulatedPhosphatidylinositol Response in Rat Cerebral CortexWalter Dixon, Yee-Way Ting, and Andi P.L. Chang 279

Blockade of High K+ Contractures and Ca + + -Dependent Slow ActionPotentials in Frog Skeletal Muscle by Opioid DrugsGeorge B. Frank and Tushar G. Kokate 283

7-Type Endorphins and Brain Dopaminergic SystemsJan M. van Ree, Jack Elands, Ildiko Kiraly, and Gerrit Wolterink 287

Cardiovascular Action of Methionine Enkephalin (MET-Enkephalin)in Conscious and Anesthetized RabbitsH.M. Rhee and S.Y. Lee 291

Respiratory Effects of Receptor-Selective Opioids in Rhesus MonkeysC.P. France and J.H. Woods 295

Regional Differences in Opioid Receptor-Mediated Inhibition of Dopamineand Acetylcholine Release in the Rat BrainM.H. Heijna, A.N.M. Schoffelmeer, and A.H. Mulder 299

Effect of Nor-Binaltorphimine on the Behavior of Mice and Rats ReceivingMultiple Injections of U-50,488Alan Cowan and Christopher W. Murray 303

Effect of Chronic Administration of Morphine and Its Withdrawal on theRat Brain and Spinal Cord Dopamine D, ReceptorsHemendra N. Bhargava and Anil Gulati 307

Contents / xiii

Brain Monoamines are Involved in the Sedative Effects of Opiates andNeurolepticsSuzanna Furst 311

Effects of Ethanol on the Brain B-Endorphin System in Inbred Strains ofMice With Variable Preference for Ethanol Solutions: In Vitro StudyJean Pascal De Waele and Christina Gianoulakis 315

Differential Contribution of the Anterior and Intermediate Pituitaryto the B-Endorphin Response to Stress in the Neonatal RatPanagoula Angelogianni and Christina Gianoulakis 319

Differential Regulation of Opioid Systems in Response to ConditionedStress in RatsBarbara Przew/ocka, Wjadys/aw Lasori, Alena Sumowa, andRyszard Przew/bcki 323

Beta-Endorphin, Human Caseomorphin, and Bovine CaseomorphinImmunoreactivity in CSF in Sudden Infant Death Syndrome and ControlsH. Storm, C.L. Reichelt, and T.O. Rognum , 327

Modification of Nociception in a Model of Localized Inflammatory Painby Long-Term Administration of NaloxoneM.J. Millan and F.C. Colpaert 331

Characterization of Putative Kappa-Opioid-Sensitive Cells of theSubstantia Nigra Pars ReticulataLisa A. Thompson and J. Michael Walker 335

Effects of Iontophoretically Applied a-Casein Exorphin on CAt

Hippocampal Field Potentials In VivoElias K. Angelopoulos, Antony Maillis, Alexandras Andreou,Elias Koutsoukos, Costas Stefanis, Spyros Loukas, and Christine Zioudrou 339

Dynorphin Prolongs the Action Potential Duration of Mouse SensoryGanglion Neurons by Decreasing a K+ Conductance Whereas theSpecific Kappa Opioid, U-50,488H, Does So by Increasing a Ca2+

ConductanceKe-Fei Shen and Stanley M. Crain 343

Opiate Receptor-Mediated Inhibition of Acetylcholine Release FromMammalian Brain: Tissue- and Species-DependencePaul A. Lapchak, Dalia M. Araujo, and B. Collier 347

Differential Activity of Selective Opioid Agonists on HypothalmicMagnocellular Neuronal ActivityGeoff Clarke, Ian Davison, Susan J. MacMillan, and D. Mark Wright 351

Interleukin-2 Interacts With Opioid Neuroregulatory Systems in theRat HippocampusDalia M. Araujo, Paul A. Lapchak, Brian Collier, and Remi Quirion 355

xiv / Contents

Effects of Opioids on Acetylcholine Release Into Fetal Vessels ofHuman Perfused Placenta! CotyledaAlan L.A. Boura, Shaun P. Brennecke, Neil M. Gude, Roger G. King,and B. Roy Krishna 359

Central p-Opiate Receptors and the Cardiac Release of Atrial NatriureticFactor (ANF)J. Szecowka, C. Campino, and J.P. Huidobro-Toro 363

Altered Plasma Leucine—Enkephalin Concentrations in Patients WithEstablished HypertensionKarin Kraft, Friedrich Kokorsch, Jorg Diehl, Rainer Kolloch, andKlaus-Otto Stumpe 367

Actions of B-Endorphin and Related Peptide Fragments on a PressorResponse Induced by Cholinergic StimulationM. Hong and K. Jhamandas 371

(+ )Naloxone Enhances Vascular Contractile Responses toAdded EpinephrineJ.L. Caffrey, S.T. Stoll, R.J. Sinclair, and B.A. Barron y 375

Prolonged Mu- and Delta-Receptor Occupancy May Result inNaloxone-Reversible Respiratory Depression and Naloxone-IrreversibleAntinociceptionEnno Freye and Gunther Schenk 379

Dermorphin Tetrapeptide Analog Induces Naloxonazine-ReversibleRespiratory StimulationPirkko Paakkari, Ilari Paakkari, and Giora Feuerstein 385

Effects of Naloxone on Pulmonary Capillary PermeabilityJ.H. Silverstein, J. Gintautas, P. Tadoori, and A.R. Abadir 389

Sufentanil-Induced Respiratory Depression in DogsP. Tadoori, R. Ravella, J.H. Silverstein, J. Gintautas, and A.R. Abadir 393

Pertussis Toxin Inhibits Morphine-Induced Release of Adenosine Fromthe Spinal CordJ. Sawynok, M. Sweeney, D. Nicholson, and T. White 397

Diuretic Profile of 66A-078, a Synthetic Non-Hydrolizable DynorphinDerivative Active CentrallyM.V. Donoso, A. P6rez, L.F. L6pez, J. Roblero, S. Tachibana, andJ.P. Huidobro-Toro 401

Morphine Enhancement of IViitogen-lnduced T-Cell ProliferationJean M. Bidlack and Lucinda M. Hemmick 405

H-Opioid-Receptor-Mediated Inhibition of D-l DopamineReceptor-Stimulated Adenylate Cyclase in Primary Cultures ofRat Neostriatal NeuronsBernard J. van Vliet, Arie H. Mulder, and Anton N.M. Schoffelmeer 409

Penicillins Exhibit Enkephalinase Inhibitory Activity in MiceS.J. Livingston, P.S. Williams, R.D.E. Sewell, and H.J. Smith 413

Contents / xv

Behavioral Effects of Endogenous or Exogenous (JA,8) Opioid Peptides:Relation With DA Mesolimbic PathwaysG. Calenco-Choukroun, V. Dauge, J. F6ger, and B.P. Roques 417

Opioid Involvement in Epileptogenic and Neurovisceral ActivityCarl Pinsky, Ranjan Bose, Arleen Hall, and Gary B. Glavin 421

Local Opioid Receptors Mediating Antinociception in Inflammation:Endogenous LigandsChristoph Stein, Christian Gramsch, Ahmed H.S. Hassan, Ryszard PrzewJocki,

1 Christopher G. Parsons, Klaus Peter, and Albert Herz 425

Does a Relationship Exist Between Stress and Opioid Dependence?Peter Oehme, Irmgard Roske, Karen Nieber, Regina Richter, Ragna Rathsack,Winfried Krause, and Augustine Minenko 429

Intracerebroventricular Analgesia Enhanced by Intrathecal (IT)Dynorphin A(l-17) AntibodyJ. Fujimoto, K. Schaus Arts, J. Rady, and L. Tseng 433

Electrophysiological Evidence That Tolerance and DependencePhenomena are Reflected at the Ventrobasal (VB) Thalamic Level inArthritic RatsValerie Kayser, Nadine Attal, YanLian Chen, and Gisele Guilbaud 437

Microinjection of 8-OH-DPAT Into Nucleus Accumbens AttenuatesNaloxone-Induced Morphine Withdrawal SyndromeMihailo R. Dzoljic, Martin v. Ent, Charles D. Kaplan, and Pramod R. Saxena.. 441

Immune Status of Unselected Methadone-Maintained FormerHeroin AddictsM.J. Kreek, E. Khuri, N. Flomenberg, H. Albeck, and M. Ochshorn 445

Modulation of the Analgesic Efficacy and Potency of Morphine by[D-PEN2, D-PEN5]Enkephalin in MiceQi Jiang, Henry I. Mosberg, and Frank Porreca 449

Naloxone Induces a Bidirectional Effect on Phasic and "Spontaneous"Pain-Related Behavior in Rats With a Peripheral MononeuropathyFre'ddrique Jazat, Nadine Attal, Valerie Kayser, and Gisele Guilbaud 453

Multiple Opioid Receptors may Mediate B-Casein-Induced Analgesiain Neonatal RatsJames Giordano and Robin Doescher 457

Opiate Analgesia and Calcium Channels Modulation by DihydropyridinesUnder Acute and Tolerant ConditionsJesus F16rez, Maria Dierssen, and Maria A. Hurle 461

Supraspinal Analgesic Action of Pentazocine in MiceHiroshi Nagase, Minoru Narita, Tsutomu Suzuki, and Miwa Misawa 465

Chronic Morphine Administration and In Vivo Pertussis ToxinTreatment Induce Hyperalgesia and Enhance 3H-Nitrendipine BindingR. Inoki, T. Ohnishi, K. Saito, S. Maeda, K. Matsumoto, and M. Sakuda 469

xvi / Contents

Antinociceptive Actions of Novel Delta Opioid Receptor Agonistsin the MouseThomas H. Kramer, Geza Toth, Elizabeth A. Ayres, Victor J. Hruby,and Thomas F. Burks 473

Morphine-6-Glucuronide is More Mu-Selective and Potent in AnalgesicTests Than MorphineBernard Franc6s, Robert Gout, G6rard Campistron, Emmanuel Panconi,and Jean Cros 477

2-Substituted-N5-(2'-Aminophenyl)-4-Thiohydantoic Acids asAminopeptidase Inhibitors With Pro-Antinociceptive ActivityZ. Yu, P.S. Williams, A. Patel, H.J. Smith, R.D.E. Sewell, andJ.P. Gonzalez 481

Peptides as Potential Antinociceptive DrugsBrendan S. Silbert, Andrzej W. Lipkowski, Daniel B. Carr,Stanislaw K. Szyfelbein, and Patricia F. Osgood 485

Effect of Panax ginseng Extract on the Pharmacological Actions ofMorphine in the RatHemendra N. Bhargava and Poduri Ramarao 489

Antagonism of Kappa Opioid-Mediated Effects in the Rat by Cyclo(Leu-Gly)Hemendra N. Bhargava and Poduri Ramarao 493

Role of Opioid Receptors hi Response to Heat Stress in Sprague-Dawley RatsH.M. Rhee and D.W. Hendrix 497

Neurochemical Aspects of Morphine Tolerance in the Freely Movingand Behaving Animal: Voltammetric StudiesPatricia A. Broderick and Frank T. Phelan 501

Release of Sensory Neuropeptides in the Cat Spinal Cord DuringMorphine WithdrawalCecil R. Morton and William D. Hutchison 507

Responses of Morphine-Dependent Opioid Neurones to StressorsJean E. Olley, George K.L. Tiong, Jane Scheer, and Nathalie M. von Jenner... 511

The Effects of Selective Dopamine D-l and D-2 Antagonists on the LocomotorResponse and Brain Monoamine Changes Induced by Naloxone-PrecipitatedMorphine Withdrawal in Guinea PigsPaul J. Brent and Loris A. Chahl 515

Physical Dependence on Morphine Using the Mu-Receptor-Deficient CXBKMouseTsutomu Suzuki and Miwa Misawa 519

Enhanced Affinity of Mu-Opioid Receptors in Morphine-Dependent MiceEssam E. Abdelhamid and A.E. Takemori 523

Effects of Chronic Treatment With Specific Antagonists on Analgesiaand Physical Dependence on Morphine in RatsYukiji Fukagawa, Tsutomu-Suzuki, Miwa Misawa, and Hiroshi Nagase 527

Contents / xvii

Naloxone-Induced Withdrawal Syndrome After Administration ofSelective Opioid Agonists or After Activation of the EndogenousEnkephalinergic SystemRafael Maldonado, Gilles Waksman, Jean Feger, and Bernard P. Roques 531

Index 535