Advances in Vasopressin and Oxytocin - From Genes to Behaviour to Disease (eBook)

Front cover 1
Progress in Brain Research 3
Copyright page 4
List of Contributors 5
Preface 11
Acknowledgements 15
Contents 17
Section I. Vasopressin and Oxytocin in Evolution, SexualDichotomy and Stress 23
Chapter 1. Nonapeptides and the evolutionary patterning of sociality 25
Nonapeptides and the patterning of behaviour 25
Deep history of the nonapeptides 26
Evolution of central nonapeptide circuits: anatomical and behavioural basics 27
Evolutionary plasticity of nonapeptide systems generates social diversity 28
Vasotocin and the evolution of avian sociality 30
Sociality and septal neuropeptides: what is being modulatedquest 31
Neuromodulatory patterning: overlapping circuits and distinct behavioural states 33
Summary 34
Abbreviations 34
Acknowledgement 34
References 34
Chapter 2. Sex differences in vasopressin and oxytocin innervation of the brain 39
Introduction 39
Causes of sex differences in AVP projections 40
Effects of circulating hormones in adulthood 40
Oestrogen versus androgen effects 40
Hormones and sex differences in AVP expression 40
Sex chromosomes in sex differences in AVP expression 41
Cellular mechanisms underlying differentiation of AVP expression 41
The origin of sexually dimorphic AVP innervation 42
Sex differences in other AVP systems 43
Function of sex differences in AVP expression 43
Lessons from spotted hyenas and prairie voles 44
Dual function for sex differences in the brain 45
Clinical implications 45
Abbreviations 45
Acknowledgement 46
References 46
Chapter 3. The parvocellular vasopressinergic system and responsiveness of the hypothalamic pituitary adrenal axis during chronic stress 51
Introduction 51
Conclusions 58
Acknowledgement 58
References 58
Section II. Genetics Meets Behaviour 63
Chapter 4. Experimental approaches for the study of oxytocin and vasopressin gene expression in the central nervous system 65
Introduction 65
Materials and methods 67
Results 70
Discussion 71
Abbreviations 72
Acknowledgements 72
References 72
Chapter 5. Oxytocin knockout mice: a model for studying stress-related and ingestive behaviours 75
Introduction 75
Methods 77
Experiments 77
Summary and implications of findings and future directions 81
Abbreviations 84
References 84
Chapter 6. The role of the vasopressin 1b receptor in aggression and other social behaviours 87
Introduction 87
Avpr1b and aggression 88
Avpr1b and social memory 89
Avpr1b and social motivation 90
Conclusions 92
Abbreviations 92
Acknowledgement 93
References 93
Chapter 7. Behavioural studies using temporal and spatial inactivation of the oxytocin receptor 95
Introduction 95
Oxt and Oxtr knockout mice 96
Behavioural analysis using conditional knockout mice 96
Phenotypical implication of Oxtr conditional knockout mice 96
Future directions 98
Abbreviations 98
Acknowledgement 98
References 98
Chapter 8. New aspects of oxytocin receptor function revealed by knockout mice: sociosexual behaviour and control of energy balance 101
Oxytocin and oxytocin receptor 101
Generation of oxytocin deficient (Oxt-/-) mice 102
Generation of oxytocin receptor deficient (Oxtr-/-) mice 103
Generation of Oxtr-Venus knockin mice to locate ‘‘Oxtr-Neurons’’ 109
Abbreviations 111
Acknowledgements 111
References 111
Section III. Regulation of Vasopressin and Oxytocin Release 113
Chapter 9. Regulation of vasopressin release by co-released neurotransmitters: mechanisms of purinergic and adrenergic synergism 115
Introduction 115
Mechanism of ATPplusPE synergism 117
Remaining issues and new hypotheses 126
Acknowledgements 127
References 127
Chapter 10. Neuron-glia interactions in the rat supraoptic nucleus 131
Introduction 131
Diffusion properties in the SON 132
Glial contribution to glutamatergic and GABAergic transmission in the SON 133
Gliotransmission in the SON and modulation of NMDA receptors 135
Conclusions 137
Abbreviations 137
Acknowledgements 138
References 138
Chapter 11. Dynamic synapses in the hypothalamic-neurohypophyseal system 141
Synaptic physiology of glutamate synapses on MNCs 142
Mechanisms responsible for asynchronous release in PVN 145
Evoked glutamate release and the regulation of MNC activity 145
Conclusions 146
Acknowledgements 148
References 148
Chapter 12. Endogenous modulators of synaptic transmission: cannabinoid regulation in the supraoptic nucleus 151
Introduction 151
The cannabinoid system in the SON 152
Future perspectives 155
Abbreviations 156
References 156
Chapter 13. Oxytocin and appetite 159
Introduction 159
Oxytocin and oxytocin-like peptides throughout evolution 160
Interactions between feeding and sex 161
Regulation of feeding in mammals 162
Oxytocin and sexual behaviour 164
The ventromedial nucleus of the hypothalamus (VMH) 165
Peptides and behaviour 168
Acknowledgements 171
References 171
Section IV. Nonapeptide Receptors: Regulation and Signalling 175
Chapter 14. Neural mechanisms underlying the milk ejection burst and reflex 177
Introduction 177
Structural considerations: the SON 178
Functional studies of milk ejection bursts and the MER 179
Functional studies of milk ejection bursts and the MER 181
Cellular mechanisms underlying OXT-induced excitation 184
Concluding remarks 186
Abbreviations 186
Acknowledgements 186
References 186
Chapter 15. Oxytocin receptor signalling 189
General thoughts on oxytocin receptor signalling 189
Novel OXTR signalling target: eEF2 192
Novel OXTR-linked signalling pathway: ERK5 194
In vitro contraction assay 195
Conclusions 196
Abbreviations 196
Acknowledgement 197
References 197
Chapter 16. Neurosteroids are excitatory in supraoptic neurons but inhibitory in the peripheral nervous system: it is all about oxytocin and progesterone receptors 199
Introduction 199
Neurosteroids: a new class of neuromodulators 200
Non-genomic effects of progestins 200
GABAA and free cytosolic Ca2›plus: a developmental pas-de-deux 202
Development of the nervous system 202
Physiological relevance of the models 208
Neuroactive steroid-signalling pathways 209
Conclusion 210
Abbreviations 211
Acknowledgements 211
References 211
Chapter 17. Oxytocin receptors: ligand binding, signalling and cholesterol dependence 215
Oxytocin 215
Oxytocin receptors 217
Oxytocin receptor research: quo vadisquest 221
Abbreviations 223
Acknowledgements 223
References 223
Section V. Neuronal Actions of Nonapeptides 227
Chapter 18. Opposite effects of oxytocin and vasopressin on the emotional expression of the fear response 229
Introduction 229
Conclusions and perspectives 236
Abbreviations 236
Acknowledgements 236
References 236
Chapter 19. Multi-factorial somato-dendritic regulation of phasic spike discharge in vasopressin neurons 241
Phasic spike discharge patterning in vasopressin neurons 241
Somato-dendritic neuropeptide release from vasopressin neurons 242
Autocrine modulation of phasic spike discharge by somato-dendritic vasopressin release 242
Autocrine modulation of phasic spike discharge by co-released neuropeptides 243
Autocrine modulation of phasic spike discharge by other factors 246
Conclusion 247
Abbreviations 248
Acknowledgements 248
References 248
Chapter 20. Neurophysiology of supraoptic neurons in C57/BL mice studied in three acute in vitro preparations 251
Introduction 251
Methods 253
Results 255
Discussion 258
Abbreviations 262
Acknowledgements 262
References 262
Chapter 21. Effects of oxytocin on GABA signalling in the foetal brain during delivery 265
GABA in the immature brain 265
Perinatal switch in the action of GABA from excitatory to inhibitory 266
Involvement of oxytocin in the perinatal GABA switch 268
Source of oxytocin in a slice preparation 268
Origin of oxytocin in the foetal brain: maternal or foetalquest 270
Oxytocin and NKCC1 271
Oxytocin as neuroprotector in perinatal hypoxia 273
Concluding remarks 274
Abbreviations 275
Acknowledgements 275
References 275
Section VI. Regulation of Social Behaviours 281
Chapter 22. Central vasopressin and oxytocin release: regulation of complex social behaviours 283
Introduction 283
Monitoring of local release of AVP and OXT during social behaviour by intracerebral microdialysis 284
Behavioural relevance of local neuropeptide release within target brain regions 287
Conclusions 293
Abbreviations 293
Acknowledgements 294
References 294
Chapter 23. Interactions between dopamine and oxytocin in the control of sexual behaviour 299
Introduction 299
Hypothalamic nuclei mediating reproductive behaviours 300
The role of oxytocin 301
The role of dopamine 301
Dopamine-oxytocin link 303
Signalling pathways 306
Conclusion 308
Abbreviations 309
Acknowledgements 309
Reference 309
Chapter 24. Steroidal/neuropeptide interactions in hypothalamus and amygdala related to social anxiety 313
Introduction 313
ERalpha compared to ERbeta 314
Social recognition and autism 315
E/OT interactions 316
A functional genomic network supporting social recognition 316
Generalized CNS arousal mechanisms related to fear 318
Hyperarousal fostering social anxiety 320
Social anxiety fostering autism 320
References 321
Chapter 25. Functional magnetic resonance imaging and the neurobiology of vasopressin and oxytocin 327
Introduction 327
Imaging conscious animals 328
Imaging aggressive motivation and the role of vasopressin neurotransmission 330
Imaging the ‘‘nursing’’ brain and the role of oxytocin neurotransmission 336
Final summary 340
References 340
Chapter 26. Evolution of the arginine vasopressin 1a receptor and implications for mammalian social behaviour 343
Introduction 343
Avpr1a: a single gene with major effect in mammals 344
Avpr1a-STRs are not evolutionary switches 345
STRs are not homologous across mammals 345
Abundant variation in the coding part of Avpr1a 347
Conclusions 350
Abbreviations 351
Acknowledgements 351
References 351
Chapter 27. Oxytocin, vasopressin and sociality 353
Introduction 353
Neuroendocrine correlates of sociality 353
Sex differences in sociality 357
Acknowledgements 357
References 357
Chapter 28. Neuropeptides and social behaviour: effects of oxytocin and vasopressin in humans 359
Introduction 359
Effects of oxytocin on human social behaviour 360
Effects of arginine vasopressin on human social behaviour 363
Clinical implications 364
Conclusion 366
Acknowledgements 368
References 369
Section VII. Oxytocin and Vasopressin: Involvement in Stress Management 373
Chapter 29. Chronic stress plasticity in the hypothalamic paraventricular nucleus 375
Activation of PVN neurons by acute stressors 377
Chronic stress: cellular responses of PVN neurons 378
Chronic stress: morphological plasticity in PVN 380
Neuroplasticity and PVN responses to chronic stress 381
Acknowledgements 383
References 383
Chapter 30. Keeping oxytocin neurons under control during stress in pregnancy 387
Introduction 387
The neurohypophysial oxytocin system and responses to stress 389
Reduced responsiveness of oxytocin neurons to stress in late pregnancy 390
Mechanisms of reduced oxytocin responses to stress in pregnancy 391
Summary 395
Abbreviations 395
Acknowledgements 396
References 396
Chapter 31. Rapid synapse-specific regulation of hypothalamic magnocellular neurons by glucocorticoids 401
Rapid glucocorticoid feedback regulation in the hypothalamus 402
Mechanisms of rapid glucocorticoid regulation of magnocellular neurons 403
Conclusion 406
Abbreviations 408
Acknowledgements 409
References 409
Chapter 32. Vasopressin in the septum: not important versus causally involved in learning and memory - two faces of the same coinquest 411
Sources and targets of intraseptal AVP 411
Stimuli for intraseptal AVP release 412
AVP signalling in the septum affects learning and memory: three examples 412
Conclusion 414
Abbreviations 416
Acknowledgements 416
References 416
Chapter 33. Role of the endocannabinoid system in regulation of the hypothalamic-pituitary-adrenocortical axis 419
Introduction 419
The endocannabinoid system 421
The hypothalamic-pituitary-adrenocortical (HPA) axis 421
Means of studying the endocannabinoid system 422
Characteristics of the endocannabinoid system at different levels of the HPA axis 424
Effects of exogenous cannabinoids on HPA axis activity 425
The role of endocannabinoid signalling for HPA axis function 430
Endocannabinoid signalling and behavioural stress coping 439
Endocannabinoid system and melancholic depression 443
Conclusion 445
Acknowledgements 445
References 446
Section VIII. Psychopathology: Critical Involvement of the Vasopressin and Oxytocin Systems 455
Chapter 34. Molecular genetic studies of the arginine vasopressin 1a receptor (AVPR1a) and the oxytocin receptor (OXTR) in human behaviour: from autism to altruism with some notes in between 457
Introduction 458
AVPR1a 458
OXTR 459
Genetic studies 460
Future directions 468
Acknowledgements 468
References 468
Chapter 35. Oxytocin and experimental therapeutics in autism spectrum disorders 473
Introduction 473
Autism spectrum disorders 474
Oxytocin and autism spectrum disorders 474
Targeting the repetitive behaviours and social cognition symptom domains 477
Future directions 480
Abbreviations 481
Acknowledgements 481
References 482
Chapter 36. Impact of prosocial neuropeptides on human brain function 485
References 490
Section IX. Vasopressin and Oxytocin Agonists and Antagonists: From Pharmacology to Clinical Utility 493
Chapter 37. Peptide and non-peptide agonists and antagonists for the vasopressin and oxytocin V1a, V1b, V2 and OT receptors: research tools and potential therapeutic agents 495
Introduction 496
Scope of the this presentation 497
Peptide synthesis 498
Bioassays 498
Receptor binding and functional assays 499
Potent andsolor selective oxytocin and vasopressin agonists 499
V1b receptor agonist development 501
Non-selective rat and human V1b/V1a antagonists 507
Cyclic and linear V2/V1a antagonists for rat VP receptors 507
V2 Antagonist with high affinity for human V2 receptor 508
Development of highly selective OT antagonists in the rat and in humans 509
OT Antagonists with high affinities and selectivities for the human OT receptor 510
Radiolabelled ligands for rat andsolor human vasopressin and oxytocin receptors 511
High affinity fluorescent agonists and antagonists for human OT and AVP receptors 512
Bivalent ligands for human and rat OT and V1a receptors 513
Non-peptide vasopressin and oxytocin antagonists and agonists 514
Non-peptide V1a receptor antagonists 514
Non-peptide V2 antagonists (Vaptans, Table 21) 516
Non-peptide V2/V1a antagonists 516
Non-peptide V1b antagonists 517
Non-peptide oxytocin antagonists 517
Non-peptide vasopressin agonists 518
Non-peptide oxytocin agonists 519
Research uses of peptide and non-peptide OT and AVP agonists, antagonists, radiolabelled ligands and fluorescent ligands 519
Species differences and lack of specificity 520
Therapeutic uses of peptide and non-peptide agonists and antagonists 520
Conclusion 521
Acknowledgements 523
References 523
Chapter 38. Affinity and efficacy of selective agonists and antagonists for vasopressin and oxytocin receptors: an ‘‘easy guide’’ to receptor pharmacology 535
Binding assays 537
Second messengers or functional studies on membranes, cells or tissues sections 537
Conclusions 538
Acknowledgements 538
References 538
Chapter 39. Prevention of hypoxic brain oedema by the administration of vasopressin receptor antagonist OPC-31260 541
Introduction 541
Methods 542
Results 543
Discussion 544
Abbreviations 546
Acknowledgements 546
References 546
Chapter 40. Characterization of a novel and selective V1B receptor antagonist 549
Introduction 549
In vitro characterization of the Organon V1b antagonist 551
In vivo characterization of the Organon V1b antagonist 551
Conclusion 556
Abbreviations 556
Acknowledgements 557
References 557
Section X. Physiology and Pathophysiology of Renal Actions of Vasopressin 559
Chapter 41. Molecular mechanisms of clinical concentrating and diluting disorders 561
Introduction 561
Congenital nephrogenic diabetes insipidus 562
Primary polydipsia 563
Hypothyroidism 563
Glucocorticoid deficiency 564
Mineralocorticoid deficiency 565
Cardiac failure 568
Cirrhosis 569
Pregnancy 570
Acknowledgements 570
References 571
Chapter 42. Actin-binding channels 573
Introduction 573
ClC2 and sClC3 chloride channel 573
V-ATPase 574
VDAC 575
ENaC 575
AQP2 575
Concluding remarks 576
Acknowledgement 577
References 577
Chapter 43. Opposite potentiality of hypothalamic coexpressed neuropeptides, apelin and vasopressin in maintaining body-fluid homeostasis 581
Structure and processing of vasopressin and apelin 581
Distribution of apelin and its receptor in the rat brain 583
Involvement of vasopressin and apelin in the maintenance of water balance 583
Vasopressin and apelin receptor subtypes involved in the control of AVP neuron activity 586
Mechanism of vasopressin release and putative mechanism of apelin release 587
Retrocontrol of AVP neuron activity 588
Involvement of vasopressin and apelin in the maintenance of water balance at the kidney level 589
Conclusion 589
Abbreviations 589
Acknowledgements 590
References 590
Chapter 44. Recent discoveries in vasopressin-regulated aquaporin-2 trafficking 593
Aquaporins and the urinary concentrating mechanism 593
Targeting mechanisms 594
Effect of arginine vasopressin 594
Role of phosphorylation 596
Role of the cytoskeleton and associated proteins 597
Role of endocytosis 598
Future perspectives 599
Acknowledgements 599
References 599
Chapter 45. Pathophysiological role of aquaporin-2 in impaired water excretion 603
Pathological states of water retention 603
AQP-2 expression in animal models 605
Tonicity regulates the AQP-2 promoter 607
Acknowledgments 609
References 609
Chapter 46. Potential utility of aquaporin modulators for therapy of brain disorders 611
Introduction 611
Aquaporins in normal brain 612
Aquaporin regulation studies 612
Roles of aquaporins in brain 613
Indications and status of aquaporin modulators 620
Perspective 621
References 621
Subject Index 625