Endogenous and Exogenous Opiate Agonists and Antagonists (eBook)

Front Cover 1
Endogenous and Exogenous Opiate Agonists and Antagonists 4
Copyright Page 5
Table of Contents 6
Preface 18
WHO ROLE IN DRUG ADDICTION 20
REFERENCES 21
PART I: Structure-Activity Relationships 22
Chapter 1. PRIMARY STRUCTURE AND SPECIFICITY IN ENDOGENOUS OPIOID PEPTIDES 24
Summary 24
REFERENCES 27
Chapter 2. SYNTHETIC ßh -ENDORPHIN ANALOGS MODIFIED AT THE N-TERMINAL, POSITIONS 2 AND 5 28
Summary 28
Methods 28
Results and Discussion 30
Acknowledgement 31
References 31
Chapter 3. CHEMICAL FEATURES FOR OPIATE AGONIST AND ANTAGONIST 32
Summary 32
Methods 33
Results and Discussion 34
References 35
Chapter 4. THE SYNTHESIS AND AGONIST ACTIVITY OF SOME 14ß-SUBSTITUTED MORPHINE AND CODEINE DERIVATIVES 36
Synthesis 36
Acknowledgements 38
References 39
Chapter 5. 4-ARYL-4-AMINOCYCLOHEXANONE DERIVATIVES: A CHEMICALLY NOVEL SERIES OF ANALGESICS INCLUDING OPIOID ANTAGONISTS AND EXTREMELY POTENT AGONISTS. 40
Summary 40
Methods 40
Results and Discussion 41
References 44
Chapter 6. N-METHYLBENZOMORPHANALKANONES. A COMPARISON OF THEIR STRUCTURE-ACTIVITY RELATIONSHIPS AND X-RAY CRYSTAL STRUCTURE WITH THOSE OF THE BRIDGED THEBAINE DERIVATIVES. AN OPIATE RECEPTOR PROPOSAL 46
Summary 46
Acknowledgement 47
References 47
Chapter 7. QUANTUM CHEMICAL STUDIES OF NOVEL 4-PHENYL PIPERIDINE OPIATES WITH ANTAGONIST ACTIVITY 48
Summary 48
Method and Procedure 48
Results and Discussion 49
Literature Cited 50
Acknowledgement 51
Chapter 8. STRUCTURE-FUNCTION STUDIES IN PEPTIDES RELATED TO THE ß-LPH61-14 SEQUENCE 52
Summary 52
Methods 52
Results and Discussion 53
REFERENCES 55
Chapter 9. Enkephalin Analogs and Physical Dependence 56
Method of Drug Delivery 56
Measurement of Withdrawal Intensity 57
Discussion 58
Acknowledgments 59
References 59
PART II: Receptor Binding 60
Chapter 10. INTERACTION OF A MODEL OPIATE ANIONIC RECEPTOR SITE WITH N-SUBSTITUENTS OF RIGID OPIATES: PCILO ENERGY CALCULATIONS 62
Summary 62
Method and Procedure 62
Results and Discussion 63
Conclusions 64
Literature Cited 64
Chapter 11. EFFECTS OF MONOVALENT CATIONS ON CEREBROSIDE SULFATE BINDING TO OPIATE AGONISTS AND ANTAGONISTS 66
Summary 66
Methods 66
Results and Discussion 67
Acknowdgement 68
References 68
Chapter 12. OPIATE BINDING AND CEREBROSIDE SULFATES IN BRAIN AND LUNG OF DEVELOPING CHICK 70
Summary 70
Methods 70
Results and Discussion 71
REFERENCES 73
Chapter 13. OPIATE RECEPTOR BINDING STUDIES INFLUENCE OF A REVERSIBLE SULFHYDRYL REAGENT 74
Summary 74
Materials and Methods 75
Results and Discussion 75
Acknowledgements 77
References 77
Chapter 14. ASCORBATE DESTRUCTION OF OPIOID STEREOSPECIFIC BINDING EVIDENCE FOR RECEPTOR REGULATION BY MEMBRANE LIPID
Summary 78
Acknowledgements 81
References 81
Chapter 15. THE STUDY OF ENKEPHALIN-RECEPTOR INTERACTION USING ISOSTERICALLY MODIFIED ANALOGUES 82
Summary 82
Methods 82
Results 82
Discussion 84
Acknowledgements 85
References 85
Addendum 85
Chapter 16. SEASONAL VARIATION IN THE APPARENT NUMBER OF 3H-NALOXONE BINDING SITES 86
Summary 86
Materials and Met 86
Results 87
Discussion 88
Acknowledgements 89
References 89
Chapter 17. EVIDENCE FOR HALF-OF-THE-SITES REACTIVITY IN THE BINDING OF OPIATE AGONISTS AND ANTAGONISTS TO THE OPIATE RECEPTOR 90
Summary 90
Materials and Metho 90
Results 91
Discussion 92
Acknowledgements 93
References 93
Chapter 18. EFFECTS OF ANESTHETICS IN VITRO ON BRAIN RECEPTORS FOR OPIATES, SPIROPERIDOL AND OUABAIN1 94
Summary 94
Materials and Methods 94
Results and Discussion 95
References 97
Chapter 19. OPIOID AGONISTS AND ANTAGONISTS: ACTION ON MULTIPLE OPIATE RECEPTORS 98
Summary 98
Methods 98
Results 99
Discussion 100
References 101
Chapter 20. STUDY OF OPIATE RECEPTOR MULTIPLICITY IN RATS BY IN VIVO BINDING ASSAYS 102
Summary 102
Methods 102
Results 103
Discussion 105
Acknowledgement 105
References 105
Chapter 21. COMPARISON OF THE BINDING CHARACTERISTICS OF OPIATES AND OPIOID PEPTIDES 106
Summary 106
Methods 106
Results 106
Discussion 107
Acknowledgements 108
References 108
Chapter 22. TYPE 1 AND TYPE 2 OPIATE RECEPTORS: A SUBCLASSIFICATION SCHEME BASEDUPON GTP'S DIFFERENTIAL EFFECTS ON BINDING 110
Summary 110
References 113
Chapter 23. SCATCHARD ANALYSIS OF OPIATE RECEPTOR BINDING 114
SUMMARY 114
INTRODUCTION 114
MATERIALS AND METHODS 114
RESULTS AND DISCUSSION 115
ACKNC^ILEDGEMENT 117
REFERENCES 117
Chapter 24. MULTIPLE OPIATE BINDING SITES IN RAT BRAIN: DIFFERENTIAL DISPLACEMENT OF 3H-NALOXONE BINDING BY DIFFERENT OPIATE LIGANDS 118
Summary 118
Methods 118
Results 119
Discussion 121
Acknowledgements 121
References 121
Chapter 25. PHENOXYBENZAMINE, AN IRREVERSIBLE LIGAND OF OPIOID RECEPTORS IN VIVO ? 122
Summary 122
Methods 122
Results 123
Discussion 124
Acknowledgements 125
References 125
Chapter 26. TOLERANCE, CROSS-TOLERANCE AND DEPENDENCETO µ AND k AGONISTS IN VIVO AND IN VITRO 126
METHODS 126
RESULTS 126
CONCLUSIONS 128
ACKNOWLEDGEMENTS 129
REFERENCES 129
Chapter 27. SPECIFIC PROTECTION OF µ- ANDd -BINDING SITES INGUINEA-PIG BRAIN, AGAINST THE INHIBITORY EFFECT OF PHENOXYBENZAMINE, BY AGONISTS PREFERENTIALLY INTER ACTING WITH µ- OR d-SITES 130
Summary 130
Materials and Methods 130
Results and Discussion 130
Acknowledgements 131
References 131
Chapter 28. LIGAND SPECIFICITY OF OPIOID BINDING SITES IN BRAIN AND PERIPHERAL TISSUES 132
Summary 132
Methods 132
Results 133
Discussion 134
Acknowledgements 135
References 135
Chapter 29. MULTIPLE OPIATE RECEPTORS: EVIDENCE FOR MEDIATION OF ANALGESIA BY A SUBPOPULATION OF RECEPTORS 136
Summary 136
Methods and Results 136
Discussion 139
Acknowledgments 139
References 139
Chapter 30. ABNORMAL BRAIN OPIATE MECHANISMS IN SCHIZOPHRENIA 140
SUMMARY 140
INTRODUCTION 140
METHODS AND RES 141
DISCUSSION 142
ACKNOWLEDGEMENTS 143
REFERENCES 143
PART Ill: Localization and Characterization of Active Sites 144
Chapter 31. CHARACTERIZATION OF 3H-ß-ENDORPHIN BINDING IN RAT BRAIN 146
Summary 146
References 148
Chapter 32. a-MSH IN BRAIN ß-ENDORPHIN NEURONS, AND OTHER NEURONS AS WELL 150
Summary 150
Methods 151
Results and Discussion 151
References 153
Chapter 33. OPIOID RECEPTOR AUTORADIOGRAPHY IN BRAINS OF HUMANS AND ANIMALS 154
Summary 154
Methods 154
Results 154
Discussion 156
Acknowledgements 157
References 157
Chpter 34. DEVELOPMENT OF OPIATE TOLERANCE/DEPENDENCE IN THE GUINEA-PIG MYENTERIC PLEXUS AND THE MOUSE VAS DEFERENS 158
Summary 158
Methods 158
Results 159
Discussion 161
References 161
Chapter 35. IONTOPHORETICALLY APPLIED MORPHINE AND MET-ENKEPHALIN MAY INTERACT WITH DIFFERENT RECEPTORS IN THE BRAIN 162
Summary 162
Methods 162
Results 163
Discussion 164
References 165
Chapter 36. LOCAL AND CNS-MEDIATED EFFECTS OF MORPHINE AND NARCOTIC ANTAGONISTS ON GASTROINTESTINAL PROPULSION IN RATS 166
Summary 166
Methds 166
Acknowledgement 169
Chapter 37. CENTRAL EFFECTS OF ß-ENDORPHIN ON INTESTINAL TRANSIT 170
Summary 170
Methods 170
Results 171
Discussion 172
Acknowledgements 172
References 172
Chapter 38. EFFECTS OF 6-HYDROXYDOPAMINE AND 5,7-DIHYDROXYTRYPTAMINE BRAINSTEM LESIONSON MORPHINE ANALGESIA IN THE RAT 174
Summary 174
Methods 175
Results 176
Discussion 177
References 177
Chapter 39. OPIOID-INDUCED HYPERMOTILITY IN RATS 178
SUMMARY 178
METHODS 179
RESULTS 179
Discussion 181
Acknowledgements 181
Chapter 40. DIFFERENCES BETWEEN THE MECHANISM OF ACTION OF MORPHINE ANTINOCICEPTION IN MICE AND RATS 182
Summary 182
Acknowledgement 185
References 185
Chapter 41. ACTIONS OF OPIOID PEPTIDES ON THE RESPONSIVENESS OF RETICULAR NEURONES TO TOOTH-PULP STIMULATION 186
Summary 186
Methods 186
Results 187
Discussion 188
Acknowledgement 189
References 189
Chapter 42. INHIBITION OF GLUTAMATE INDUCED CORTICAL RELEASE OF ADENINE DERIVATIVES BY OPIATES AND ENKEP 190
Summary 190
Methods 190
Results 191
Discussio 192
Acknowledgements 193
References 193
Chapter 43. INTRASTRIATAL INJECTION OF MORPHINE: EFFECT ON EMG-RECORDED ACTIVITY OF THE GASTROCNEMIUS-SOLEUS MUSCLE OF RATS 194
Summary 194
Methods 194
Results and Discussion 195
Acknowledgements 197
Reference 197
Chapter 44. EEG ALTERATIONS INDUCED IN RATS BY ETHYLKETOCYCLAZOCINE, CYCLAZOCINE, AND MORPHINE: THE DIFFERENTIAL EFFECTS OF NALOXONE 198
Summary 198
Methods 198
Results 199
Discussion 200
Acknowledgments 201
References 201
Chapter 45. ONTOGENESIS OF ENKEPHALINERGIC SYSTEMS IN RAT BRAIN 202
Summary 202
Materials and Methods 202
Results and Discussion 203
References 205
Chapter 46. IMMUNOHISTOCHEMICAL LOCALIZATION OF METHIONINE ENKEPHALIN IN OLD WORLD PRIMATES: PRELIMINARY OBSERVATIONS 206
Summary 206
Methods 206
Results and Conclusions 207
References 209
Chapter 47. ENDORPHIN AND CORTICOTROPIN REGULATE THE ACTIVITY OF SEPTAL-HIPPOCAMPAL CHOLINERGIC NEURONS 210
Summary 210
Acknowledgement 212
References 212
Chapter 48. NALOXONE EXCITATION OF SPINAL DORSAL HORN UNITS SHOWS DIURNAL VARIATION 214
Methods 214
Results 215
Discussion 216
Ackowledgments 217
References 217
PART IV: Ligands and Receptor Isolation 218
Chapter 49. PARTIAL PURIFICATION OF ENDORPHINS FROM HUMAN CEREBROSPINAL FLUID FROM CHRONIC BACK PAIN AND ELECTIVE SURGERY PATIENTS 220
Summary 220
Methods 220
Results 221
Discussion 222
Acknowledgements 223
References 223
Chapter 50. IDENTIFICATION OF A NEW OPIOID PEPTIDE FROM THE BOVINE BRAIN AND ITS MECHANISM OF ACTION 224
Summary 224
Methods 224
Results and Discussion 225
Acknowledgements 227
References 227
Chapter 51. ACUPUNCTURE TOLERANCE I N RATS: ANTI-OPIATE SUBSTRATES IMPLICATED 228
Summary 228
Methods 228
Results 229
Discussion 231
References 231
Chapter 52. STUDIES ON POSSIBLE PRECURSORS FOR THE ENKEPHALINS 232
INTRODUCTION 232
MATERIALS AND METHODS 232
RESULTS 233
DISCUSSION 234
REFERENCES 235
Chapter 53. ENKEPHALIN PRECURSORS FROM GUINEA-PIG MYENTERIC PLEXUS 236
Summary 236
Methods 236
Results 237
Discussion 238
Acknowledgem 239
References 239
Chapter 54. CHARACTERIZATION OF HIGH MOLECULAR WEIGHT ENKEPHALIN IMMUNOREACTIVITY IN RAT BRAIN AND BOVINE ADRENAL MEDULLA 240
Summary 240
Materials and Methods 240
Results 241
DISCUSSION 243
Acknowledgements 243
References 243
Chapter 55. TENTATIVE SUBUNIT COMPOSITION OF ENKEPHALIN-MACROMOLECULE COMPLEXEX 244
Summary 244
RESULTS 245
Discussion 246
Acknowledgemenrs 247
References 247
Chapter 56. CHARACTERIZATION OF A HIGH AFFINITY 3H-ßh-ENDORPHIN RECEPTOR IN RATBRAIN CRUDE SYNAPTOSOMAL FRACTION 248
Summary 248
Results 249
Discussion 251
References 251
Chapter 57. ENDOKPHIN-REGULATED PROTEIN PHOSPHORYLATION AS A FUNCTIONAL ENTITY OF THE OPIATE-RECEPTOR COMPLEX 252
SUMMARY 252
METHODS 253
RESULTS AND DISCUSSI 253
REFERENCES 255
Chapter 58. ß-CAS0M0RPHINS - NOVEL OPIOID PEPTIDES DERIVED FROM BOVINE CASEIN- ISOLATION AND STRUCTURE 256
Summary 256
References 259
PART V: Neurochemical Interactions 260
Chapter 59. THE EFFECT OF OPIOIDS ON THE PHOSPHORYLATION 'IN VITRO' OF SYNAPTIC MEMBRANE PROTEINS 262
Summary 262
Materials and Meth 263
Results 263
Discussion 264
References 265
Chapter 60. ß-LIPOTROPIN, CORTICOTROPIN AND ß-ENDORPHIN: PHOSPHORYLATION BY CYCLIC AMP-DEPENDENT AND INDEPENDENT PROTEIN KINASES 266
Summary 266
Acknowledgements 269
References 269
Chapter 61. PHOSPHORYLATION OF ENDOGENOUS ß-LIPOTROPIN AND OTHER PEPTIDES BY SLICESOF PITUITARY, ADULT BRAIN AND NEONATE BRAIN OF THE RAT 270
Summary 270
Acknowledgements 273
References 273
Chapter 62. THE ROLE OF Na+AND GTP IN NG108-15 OPIATE RECEPTOR FUNCTION 274
Summary 274
Methods 274
Results and Disc 275
References 277
Chapter 63. GROWTH INHIBITION INDUCED BY METHADONE: PREVENTION BY DIBUTYRYL CYCLIC ADENOSINE MONOPHOSPHATE 278
SUMMARY 278
Materials and Methods 278
Results 279
Discussion 280
References 281
Acknowledgement 281
Chapter 64. CALCIUM IONS AND OPIOID ACTION IN NEUROBLASTOMA X GLIOMA HYBRIDCELLS 282
Summary 282
Results 282
Discussion 284
Acknowledgement 285
References 285
Chapter 65. CALCIUM ANTAGONISM OF OPIATE ACTION IN THENON-TOLERANT AND TOLERANT GUINEA PIG ILEUM 286
Summary 286
Results 287
Discussion 288
Acknowledgements 289
References 289
Chapter 66. OPIOID-INDUCED CHANGES IN CELL SURFACE COMPOSITION OF NEUROTUMOR CELL LINES 290
Summary 290
Acute Effects of Opiat 290
Discussion 293
Acknowledgements 293
References 293
Chapter 67. A ROLE OF LIPID IN OPIATE-RECEPTOR INTERACTION 294
SUMMARY 294
MATERIALS 294
METHODS 295
RESULT AND DISCUSSION 295
REFERENCES 297
Chapter 68. POTENTIATION OF OPIATE EFFECTS IN THE NEUROBLASTOMA CELL LINE N18TG-2 BY SULFATIDE INCORPORATION 298
Summary 298
Materials and Methods 299
Discussion 301
Acknowledgements 301
References 301
Chapter 69. SEARCH FOR A "SODIUM EFFECT" IN THE ACTION OF OPIATES ON HUMAN PLASMA CHOLINESTERASE 302
Summary 302
Introduction 302
Methods 303
Results 303
Discussion 304
References 304
PART VI: Disposition and Metabolism 306
Chapter 70. RELEASE OF ENDORPHINS AND THEIR MODULATION FROMRAT BRAIN IN VITRO 308
Summary 308
Methods 308
Acknowledgements 311
References 311
Chapter 71. IN VITRO BIOSYNTHESIS AND CHEMICAL CHARACTERIZATION OF ACTH AND ACTH FRAGMENTS BY THE RAT PARS INTERMEDIA 312
Summary 312
Methods 312
Results 313
Discussion 314
Acknowledgement 315
Chapter 72. MATURATION OF THE COMMON PRECURSOR FOR BETA-ENDORPHIN AND ALPHA-MSH IN THE RAT PARS INTERMEDIA 316
Summary 316
Methods 316
Results 317
Conclusion 318
References 319
Chapter 73. PAIN THRESHOLD AND BRAIN ENDORPHIN LEVELS IN GENETICALLY OBESE (ob/ob) AND OPIATE RECEPTOR DEFICIENT (CXBK) MICE 320
SUMMARY 320
INTRODUCTION 320
MATERIALS AND METHODS 321
RESULTS 321
DISCUSSION 323
ACKNOWLEDGEMENT 323
REFERENCES 323
Chapter 74. SPECIFIC PROCESSING OF ENDORPHINS IN RAT BRAIN 324
Materials and Methods 348
Results 325
Discussion 327
Acknowledgement 328
References 328
Chapter 75. LASMA LEVELS OF B-ENDORPHIN/B-LIPOTROPIN IN HUMANS UNDER STRESS 329
Summary 329
Methods 329
Results 330
Discussion 330
References 330
Chapter 76. THE OCCURRENCE OF ß-ENDORPHIN AND OF ALPHA-MELANOTROPIN IN THE SECRETORY GRANULES OF ANTERIOR PITUITARY CORTICOTROPIN/ENDORPHIN CELLSMAY BE COUPLED 331
SUMMARY 331
MATERIALS AND METHODS 332
RESULTS 332
DISCUSSION 332
ACKNOWLEDGEMENT 334
REFERENCES 334
Chapter 77. CORTICOTROPIN, B-LIPOTROPIN/B-ENDORPHIN AND THE NON-CORTICOTROPIN/B-LIPOTROPIN PORTION OF THEIR COMMON PRECURSOR ARE PRESENT IN THE SAME SECRETORY GRANULES 335
SUMMARY 335
MATERIALS AND METHODS 335
RESULTS AND DISCUSSION 337
ACKNOWLEDGEMENT 337
REFERENCES 337
Chapter 78. HUMORAL ENDORPHIN: ENDOGENOUS OPIATE IN BLOOD CEREBROSPINAL FLUID AND BRAIN 339
Summary 339
Methods 339
Results 339
Discussion 340
References 342
Chapter 79. DEMONSTRATION OF PLACENTAL ENDORPHINS BY RADIOIMMUNOASSAY AND RADIORECEPTOR TECHNIQUES 343
SUMMARY 343
METHODS 343
RESULTS 344
DISCUSSION 346
ACKNOWLEDGEMENTS 346
REFERENCES 346
Chapter 80. INCREASED BIOSYNTHESIS OF ß-ENDORPHIN IN THE PARS INTERMEDIA OF RAT PITUITARIES AFTER LONG-TERM TREATMENT WITH HALOPERIDOL 347
Summary 347
Material and Methods 347
Results 350
References 351
Chapter 81. BIOSYNTHESIS OF BETA-ENDORPHIN AND ALPHA-MSH IN THE PARS INTERMEDIA OF RAT PITUITARIES 352
Summary 352
Materials and Methods 352
Results 353
Cone!usion 354
References 355
Chapter 82. ENDORPHIN LEVELS IN THE RAT BRAIN AFTER THE TOOTH PULP STIMULATION 356
Summary 356
Methods 356
Results and Discussi 357
Conclusion 359
Reference 359
Chapter 83. IN VITRO EVIDENCE FOR AN INVOLVEMENT OF INTESTINAL ENDORPHINS IN THE CONTROL OF PERISTALSIS IN THE GUINEA PIG ILEUM. COMPARISON TO RABBIT, RAT, CAT AND DOG SMALL INTESTINE. 360
Summary 360
Materials and methods 360
Results and discussion 361
References 363
Acknowledgements 363
Chapter 84. Using HPLC and fluororaetric methodsin studying endogenous peptides 364
Summary 364
Methods 364
Results 365
Discussion 366
References 367
Chapter 85. CHARACTERIZATION OF ENKEPHALINA 368
Results 369
Discussion 370
References 371
Chapter 86. FURTHER CHARACTERISATION AND KINETICS OF APPEARANCE OF HYDROLYSIS PRODUCTS OF MET-ENKEPHALIN 372
Summary 372
Methods 373
Results and discussion 373
References 375
Chapter 87. DEGRADATION OF ENKEPHALIN BY TWO BRAIN ENZYMATIC ACTIVITIES 376
Summary 376
Materials and Methods 376
Results and Discussion 377
References 379
Chapter 88. ENKEPHALINASE: PRELIMINARY CHARACTERIZATION AND COMPARISON WITH ANGIOTENSIN CONVERTING ENZYME 380
Summary 380
Methods 380
Results 380
Discussio 382
References 383
PART VII: Analgetic Mechanisms 384
Chapter 89. ANTAGONISM OF MORPHINE ACTION BY CEREBROSIDE SULFATE ANTIBODY 386
Summary 386
Methods 386
Results 387
Discussion 388
Acknowledgements 388
References 388
Chapter 90. ONE WAY CROSS TOLERANCE FROM MORPHINE TO NANTRADOL - A POTENT, NON-OPIOID ANALGETIC 390
Summary 390
Introduction 390
Methods 390
Acknowledgements 393
References 393
Chapter 91. ORAL TRYPTOPHAN AS A POTENTIAL ADJUNCTIVE THERAPY IN CHRONIC PAIN PATIENTS 394
Summary 394
Methods 395
Results 395
Discussion 396
Acknowledgements 397
Reference 397
Chapter 92. DIETARY SUPPLEMENTATION WITH L-TRYPTOPHAN REVERSES TOLERANCE TO ANALGESIA INDUCED BY PERIAQUEDUCTAL GRAY STIMULATION IN HUMANS 398
Summary 398
Methods 398
Comment 400
Acknowledgemen 400
References 401
Chapter 93. FURTHER STUDIES ON THE ANALGESIC ACTIVITY OF D-PHENYLALANINE (DPA) IN MICE AND HUMANS 402
Summary 402
Materials and Method 402
Results 403
Discussion 405
References 405
Chapter 94. THE ANTlPEPTIDASES INCREASE ELECTROACUPUNCTURE ANALGESIA AND SHOW PREDICTABLE HYPALGESIC EFFECTS ON MICE WITH CONGENITALLY ABNORMAL ENDORPHIN SYSTEMS 406
Summary 406
Methods 406
Discussion 409
Acknowledgement 409
Reference 409
Chapter 95. BIPHASIC DOSE RESPONSE TO BUPRENORPHINEIN THE RAT TAIL FLICK ASSAY: EFFECT OF NALOXONE PRETREATMENT 410
Summary 410
Results 411
References 413
Chapter 96. IS ß-ENDORPHIN INVOLVED IN THE ANALGESIA GENERATED BY STRESS? 414
Summary 414
Methods 415
Results and Discussion 415
References 417
Chapter 97. CENTRAL 5-HYDR0XYTHYPTAMINE, OPIATE-LIKE SUBSTANCES AND ACUPUNCTURE ANALGESIA 418
summary 418
Chapter 98. ULTRAVIOLET RADIATION-INDUCED NOCICEPTION: BASIS FOR A NOVEL ANALGESIC TEST IN MICE 422
Summary 422
Conclusions 424
Acknowledgements 425
References 425
PART VIII: Neuroendocrine Relationships 426
Chapter 99. ESTROGEN TREATMENT ALTERS NARCOTIC DISPOSITION IN THE RAT 428
Summary 428
Methods 428
Results 429
Discussion 429
Acknowledgments 429
References 430
Chapter 100. EFFECTS OF MORPHINE ON SERUM PROLACTIN LEVELS AND DOPAMINE TURNOVER IN THE MEDIAN EMINENCE: ACUTE AND CHRONIC EFFECTS 432
Summary 432
Methods 432
Results 433
Discussion 434
Acknowledgments 435
References 435
Chapter 101. THE EFFECT OF ACUTE ADMINISTRATION OF MORPHINE AND OPIATE ANTAGONISTS ON THE INDOLE CONTENT OF THE RAT PINEAL GLAND 436
Summary 436
Materials and Methods 437
Results 437
References 439
Chapter 102. CHANGES INDUCED BY AN OPIOID ON BLOOD GLUCOSE AND INSULIN IN THE RAT 440
Summary 440
Methods 440
Results and discussion 441
References 443
Chapter 103. NARCOTIC ANTAGONISTS INCREASE SERUM LUTEINIZING HORMONE LEVELS BY A NONTESTOSTERONE-DEPENDENT MECHANISM 444
Summary 444
Methods 445
Results 445
Discussion 446
Acknowledgment 447
PART IX: Behavioral Effects 448
Chapter 104. NALOXONE'S EFFECTS ON A VARIETY OF MOTIVATED BEHAVIORS 450
Summary 450
Intracranial Reinforc 450
Sexual Behavior 451
Ingestive Behavi 451
Discussion 452
Acknowledgements 453
References 453
Chapter 105. THE ACTIVATION OF ENDORPHIN(S) BY REWARD 454
Summary 454
Results and Discuss 454
Acknowledgements 457
References 457
Chapter 106. DISCRIMINATION OF THE INTEROCEPTIVE STIMULI PRODUCED BY PHENYL-QUINONE. A MEASURE OF THE AFFECTIVE COMPONENT OF PAIN IN THE RAT 458
Summary 458
Methods 458
Results 459
Discussion 461
References 461
Chapter 107. GENERALIZATION STUDY WITH SOME NARCOTIC AND NONNARCOTIC PSYCHOACTIVE DRUGS IN RATS TRAINED TO DISCRIMINATE BETWEEN CYCLAZOCINE AND SALINE 462
SUMMARY 462
INTRODUCTION 462
METHODS 462
RESULTS 463
DISCUSSION 465
REFERENCES 465
Chapter 108. DISCRIMINATIVE AND REINFORCING EFFECTS OF SOME SYSTEMICALLY ACTIVE ENKEPHALIN ANALOGUES 466
Summary 466
Methods 467
Results and Discuss 467
Acknowledgments 468
References 468
Chapter 109. NALOXONE ANTAGONISM OF MORPHINE-WITHDRAWAL BODY SHAKES BY AN AUDITORY CONDITIONAL STIMULUS 470
SUMMARY 470
METHODS 470
RESULTS 471
DISCUSSION 472
ACKNOWLEDGEMENT 473
REFERENCES 473
Chapter 110. POSSIBLE GABA INVOLVEMENT IN THE MEDIATION OF NARCOTIC ANTAGONIST-INDUCED AVERSIONS 474
Results 475
Discussion 477
References 477
Acknowledgement s 477
Chapter 111. ENDOGENOUS OPIATES AS MEDIATORS OF ACTIVATION AND COPING 478
Summary 478
Introduction 478
Experimental Methods of Procedure 479
Results 479
Discussion 481
Acknowledgments 481
References 481
Chapter 112. SIMILARITY BETWEEN BEHAVIORAL EFFECTS OF DES-TYROSINE-y-ENDORPHIN AND HALOPERIDOL AND OF a-ENDORPHIN AND AMPHETAMINE 482
Summary 482
Open field behavior 483
Behavioral profile 483
Concluding remar 485
References 485
Chapter 113. DIURNAL DIFFERENCES IN ENKEPHALIN LEVELS CORRELATED WITH NOCICEPTIVE SENSITIVITY 486
Summary 486
Hypophysecto 487
Results 487
Acknowledgements 489
References 489
Chapter 114. ENDORPHIN-LIKE RESPONSES PROVOKED BY INTRACEREBROVENTRICULAR PEPTIDASE INHIBITORS IN MILDLY STRESSED RATS 490
Summary 490
Materials and Methods 490
Results 491
Discussion 492
Acknowledgements 493
References 493
Chapter 115. ACTIONS OF HYPERALGESIC SUBSTANCES {(-)NALOXONE, THEOPHYLLINE AND 5-METHOXY-N,N-DIMETHYLTRYPTAMINE} ON NOCICEPTIVE LEARNING 494
Summary 494
Methods 494
Discussion 496
Acknowledgements 497
References 497
Chapter 116. THE EFFECT OF PROTOTYPE OPIATE RECEPTOR AGONISTS AND OPIOID PEPTIDES ON BODY TEMPERATURE AND BEHAVIOUR AFTER CENTRAL ADMINISTRATION TO CATS 498
Summary 498
Results 499
Discussion 501
References 501
Chapter 117. NALOXONE IMPROVEMENT OF SHOCK PATHOPHYSIOLOGY: EVIDENCE FOR OPIATE RECEPTOR INVOLVEMENT 502
Summary 502
Results 503
Discussion 503
Acknowledgements 505
References 505
Chapter 118. NALOXONE REVERSAL OF HYPOTENSION CAUSEDBY SPINAL TRANSECTION 506
Summary 506
Materials and Methods 506
Results 507
Discussion 507
Acknowledgements 509
References 509
Chapter 119. ELECTROCONVULSIVE SHOCK (ECS) IN RATS: NALOXONE MODIFICATION OF POST-ECS BEHAVIORS PROVIDES EVIDENCE FOR FUNCTIONAL ENDORPHIN RELEASE 510
Summary 510
Materials and Methods 510
Results 511
Discussion 511
Acknowledgements 513
References 513
PART X: Tolerance and Physical Dependence 514
Chapter 120. EVIDENCE FOR BIOCHEMICAL ADAPTATION IN MORPHINE TOLERANCE DEPENDENCE 516
Summary 516
Results 517
Discussion 518
References 519
Chapter 121. Serotonin-Substance-P Pathway in the Manifestation of Gut With 520
Summary 520
Methods 520
Result 520
Discussion 522
References 523
Chapter 122. DEVELOPMENT OF TOLERANCE TO AND DEPENDENCE ON OPIOIDS IN THE ISOLATED LONGITUDINAL MUSCLE STRIPS OF GUINEA PIG ILEUM 524
SUMMARY 524
METHOD 524
RESULTS 525
DISCUSSION 527
REFERENCES 527
Chapter 123. LACK OF DEPENDENCE LIABILITY OF DEZOCINE (WY-16225) IN THE MYENTERIC PLEXUS-LONGITUDINAL MUSCLE STRIP OF GUINEA PIG ILEUM 528
Summary 528
Methods 528
Results 529
Discussion 530
References 531
Chapter 124. TOLERANCE, DEPENDENCE AND QUASI-DEPENDENCE IN THE GUINEA-PIG ISOLATED ILEUM 532
Summary 532
Methods 532
Results 533
Discussion 535
Acknowledgement 535
References 535
Chapter 125. INTERACTIONS BETWEEN CLONIDINE AND A WITHDRAWAL-INDUCING BENZAZOCINE UPON THE ISOLATED MOUSE VAS DEFERENS AND GUINEA-PIG ILEUM 536
Summary 536
Method 537
Results 537
Acknowledgements 539
References 539
Chaptet 126. AN EXAMINATION OF TOLERANCE TO THE ANTINOCICEPTIVE EFFECTS OF MORPHINE, CLONIDINE AND THEIR COMBINATION IN THE MOUSE TAIL IMMERSION TEST 540
SUMMARY 540
Materials and Methods 540
Results 541
References 543
Chapter 127. DIFFERENTIAL EFFECTS OF LEU- AND MET-ENKEPHALIN ON NARCOTIC-INDUCED ENHANCEMENT OF NALOXONE EFFICACY 544
Summary 544
Methods and Materials 544
Results 545
Discussion 546
Acknowledgement 547
References 547
Chapter 128. EXAGGERATED WEIGHT LOSS IN GENETICALLY OBESE (ob/ob) MICE BY WITHDRAWAL FROM MORPH 548
Summary 548
Methods 548
Results 551
Discussion 551
Acknowledgement 551
References 551
Chapter 129. N-DEALKYLATION IN THE CNS: EFFECT OF TOLERANCE AND OPIATE ANTAGONISTS 552
Summary 552
Materials and Methods 552
Results and Discussion 553
Acknowledgement 554
References 555
Chapter 130. ELECTROACUPUNCTURE HYPALGESIA IS ENHANCED IN MORPHINE DEPENDENT MICE SHOWING NO CROSS-TOLERANCE AND REDUCING SIGNS OF WITHDRAWAL
Summary 556
Method 556
Result 556
Discussion 558
Acknowledgement 558
Reference 558
Chapter 131. STUDY OF CROSS-TOLERANCE TO THE EFFECTS OF MORPHINE AND METHADONE ON THE EEG AND BEHAVIOR OF THE L-ALPHA-ACETYLMETHADOL (LAAM)-MAINTAINED RAT 560
Summary 560
Methods and Proce 560
Results 561
Discussio 562
References 562
Chapter 132. DEVELOPMENT OF TOLERANCE TO OPIATES IN EXPU/NTS OF MOUSE SPINAL CORD WITH ATTACHED DORSAL ROOT GANGLIA 564
Summary 564
Methods 565
Results and Discussion 565
Acknowledgements 567
References 567
Chapter 133. THE EFFECTS OF MELANOCYTE-STIMULATING HORMONE RELEASE INHIBITING FACTOR AND SYNTHETIC ANALOGS ON TOLERANCE TO AND PHYSICAL DEPENDENCE ON MORPHINE 568
Summary 568
Methods and Materials 568
Results 569
Acknowledgements 571
References 571
Chapter 134. MODIFICATION OF DEVELOPMENT OF PHYSICAL DEPENDENCE ON MORPHINE BY THYROTROPIN-RELEASING HORMONE 572
Summary 572
Materials and Methods 572
Results 573
Discussion 574
Acknowledgements 575
References 575
Chapter 135. INHIBITION OF TOLERANCE TO MORPHINE BY {DPhe }-ACTH(1-10)-NH2 576
Summary 576
Materials and Metho 576
Results 577
Discussion 577
References 579
Chapter 136. DEPENDENCE IN NON-ADDICT HUMANS AFTER A SINGLE DOSE OF MORPHINE 580
Summary 580
Methods 581
Results 582
Discussion 582
References 583
Chapter 137. OPIATES AND SOCIAL DEPENDENCE 584
CONCLUSION 586
REFERENCES 587
Chapter 138. REVERSAL OF CLONIDINE-INDUCED HYPOTENSION BY OPIOID ANTAGONISTS 588
Summary 588
Results and Discussion 589
Author Index 590