Quantum Physics of Time:: Cosmology, Brain, Mind, and Time Travel

Copyright......Page 1
Dedication......Page 2
Preface......Page 3
List of Contributors......Page 5
Color Plates......Page 8
Introduction......Page 22
Photosynthesis......Page 23
A mino acid......Page 24
Tryptophan derivatives......Page 26
Primitive hydroxylase enzymes......Page 28
Presence of serotonin......Page 29
The Animal Kingdom ( Table 2 )......Page 30
Receptors......Page 31
Trophic......Page 33
Seasonal affective disorder and suicides......Page 34
Summary......Page 35
References......Page 36
Introduction......Page 42
5- HT 1 receptor genes......Page 43
5-HT 2 receptor genes......Page 46
5-HT 3 receptor genes......Page 48
5-HT 4 receptor genes......Page 49
5-HT 5 receptor genes......Page 50
Tryptophan hydroxylase genes......Page 51
Tryptophan hydroxylase 2 gene ( TPH-2 )......Page 52
Serotonin transporter gene ( SERT , 5-HTT , SLC6A4 )......Page 54
Brain-derived neurotrophic factor gene ( BDNF )......Page 55
Monoamine oxidase genes ( MAO )......Page 56
A cknowledgements......Page 58
References......Page 59
Introduction......Page 70
Caudal linear nucleus......Page 71
(b) The serotonergic neurons of the pontomesen cephalic reticular formation......Page 72
Connectivity......Page 73
Efferent projections from the rostral group......Page 74
Afferent projections to the rostral group......Page 76
Efferent projections from the caudal group......Page 77
References......Page 78
Introduction......Page 84
Cerebral cortex......Page 90
Basal forebrain......Page 92
Neostriatum......Page 93
Nucleus accumbens......Page 94
Globus pallidus......Page 95
Subthalamic nucleus......Page 96
Hypothalamus......Page 97
Circumventricular organs......Page 99
Supra-ependymal plexus......Page 100
V entral tegmental area......Page 101
Superior colliculus......Page 102
Nucleus raphe dorsalis......Page 103
Mesopontine tegmentum......Page 104
Facial motor nucleus......Page 105
Dorsal column nuclei......Page 106
5-HT innervation of the spinal cord......Page 107
References......Page 109
Introduction......Page 121
The four pharmacologically defined 5-HT receptor classes......Page 122
G-protein-coupled receptors......Page 123
Genomic, post-genomic characteristics of 5-HT receptors......Page 124
Editing......Page 125
5-HT 2A receptors......Page 127
Non-G-protein dependent signaling......Page 129
A gonist-directed signaling......Page 130
Toward the notion of a 5-HT receptor complex......Page 131
5-HT 3 receptor signaling......Page 134
References......Page 135
5-HT 1A receptors......Page 140
5-HT 1B receptors......Page 141
5-HT 1D receptors......Page 143
5-HT 1F receptors......Page 144
5-HT 2C receptors......Page 145
5-HT 3 receptors......Page 146
5-HT 4 receptors......Page 147
5-ht 5a receptors......Page 148
5-HT 7 receptors......Page 149
References......Page 150
Introduction......Page 156
Microdialysis......Page 157
V oltammetry......Page 159
SERT tracer ligands and PET applications in animals and humans......Page 160
Ligands for serotonin receptors for use with PET......Page 161
Tryptophan depletion and the measurement of serotonin function......Page 162
Conclusions......Page 163
References......Page 164
Introduction......Page 167
Response to stressors......Page 168
A utonomic function......Page 170
Motor activity......Page 171
Fatigue......Page 173
Discussion......Page 174
References......Page 175
Introduction......Page 177
Hippocampal 5-HT 1A receptors: modulation by antidepressant drugs......Page 178
5-HT 1A receptors and the basal ganglia......Page 179
5-HT 1B receptors......Page 180
5-HT 2A receptors......Page 181
5-HT 2A receptors enhance mPFC glutamate release......Page 182
Challenges to presynaptic thalamocortical 5-HT 2A receptors......Page 184
5-HT 2C receptors......Page 185
Hippocampal 5-HT 3 receptors in interneurons......Page 186
5-HT 3 receptors and dopamine-containing midbrain cells......Page 187
5-HT 4 receptors......Page 188
Hippocampal 5-HT 7 receptors......Page 189
Summary......Page 190
References......Page 191
Serotonin biosynthesis......Page 197
Factors responsible for TPH activity in vivo......Page 198
BH 4 requirement......Page 200
TPH as an iron enzyme......Page 202
Activation of TPH, or restoration of the lost activity of TPH......Page 203
Unique iron requirement of TPH......Page 204
Availability of ferrous iron in the cell......Page 206
TPH protein turnover......Page 207
Involvement of TPH in neural development......Page 208
Effect of TPH on behavioral traits......Page 209
Notes......Page 210
References......Page 211
Introduction: pathways of serotonin degradation......Page 217
MAO: general characteristics......Page 218
MAO isoenzymes......Page 219
Localization and distribution of MAO......Page 221
Role of MAO in behavioral regulation: pharmacological inhibition......Page 222
MAO polymorphisms......Page 223
MAO A knockout mice......Page 224
References......Page 226
Introduction......Page 233
The hippocampus......Page 234
Pyramidal cells......Page 235
GABAergic interneurons......Page 236
The cerebral cortex......Page 238
Pyramidal cells......Page 239
Interneurons......Page 240
Serotonergic regulation of cortical synaptic plasticity......Page 241
A cknowledgements......Page 242
References......Page 243
5-HT autoreceptors......Page 246
A ntidepressant augmentation using 5-HT autoreceptor antagonists......Page 247
Physiological and pathophysiological effects of 5-HT autoreceptors......Page 248
Feedback involving postsynaptic 5-HT 1A receptors......Page 249
Feedback involving postsynaptic 5-HT 2 receptors......Page 250
Neural pathways involved in postsynaptic 5-HT feedback......Page 251
LHb – DRN pathways and postsynaptic 5-HT feedback......Page 252
Possible physiological roles of postsynaptic 5-HT feedback......Page 253
Novel therapeutic strategies exploiting postsynaptic feedback......Page 254
References......Page 255
Tryptophan depletion......Page 261
Effects of tryptophan depletion on 5-HT release and neuronal activity......Page 262
Other effects of tryptophan depletion – alternative mechanisms......Page 264
Peripheral processes......Page 265
Consequences for the interpretation of tryptophan-depletion induced effects......Page 266
References......Page 267
Introduction......Page 271
Influence of 5-HT receptors on brain noradrenaline......Page 272
Influence of 5-HT receptors on brain dopamine......Page 273
GABA......Page 278
Glutamate......Page 279
Projection from prefrontal cortex to raphe nuclei: crossroad of multiple receptors and transmitters......Page 280
References......Page 281
Serotonergic systems of the brainstem......Page 289
A scending projections of the dorsal raphe nucleus......Page 290
DRN projections to the basal forebrain......Page 291
Differential serotonergic DRN and MRN projections to the septum and hippocampus......Page 292
Recent examination of the effects of MRN stimulation on the hippocampal EEG and hippocampal unit activity......Page 294
Unit activity in the median raphe nucleus in relation to the hippocampal EEG – serotonergic and non-serotonergic neurons......Page 295
Functional significance of theta and by inference the functional role of MRN-elicited blockade of theta- or the desynchronization (non-theta) of the hippocampal EEG......Page 299
Unit activity in the dorsal raphe nucleus (DRN) in relation to the hippocampal EEG (serotonergic and non-serotonergic neurons) and possible functional roles......Page 300
References......Page 301
The 5-HT system stimulates respiratory output......Page 305
The 5-HT system is involved in the response to hypercapnia......Page 306
5-HT neurons have cellular properties consistent with a role as CRCs......Page 307
Respiratory output and chemoreception are altered by interfering with the 5-HT system......Page 308
Role of 5-HT neurons in forebrain effects of hypercapnia......Page 309
SIDS......Page 310
SUDEP......Page 311
Panic disorder......Page 312
References......Page 313
Serotonin cell determination......Page 318
Development of the serotonergic system in rodent models......Page 319
A utocrine/autoregulatory effects......Page 320
Gliogenesis and maturation......Page 321
A xonal elongation......Page 322
1 – 3 weeks rat: first 2 years of human life......Page 323
Stress......Page 324
Summary......Page 325
References......Page 326
Methodological considerations in brain/behavior analyses......Page 333
Serotonin and motoric function......Page 335
Serotonin and sensory – motor reactivity......Page 336
References......Page 337
Introduction......Page 339
Serotonin and feeding behavior: early studies wit hhuman participants......Page 340
5-HT 1B and 5-HT 2C receptors and feeding......Page 341
5-HT 6 receptors and feeding......Page 344
Neural mechanisms underpinning serotonergic modulation of feeding behavior......Page 345
Serotonin – CCK interactions......Page 347
References......Page 349
Introduction......Page 354
Implications for a role of 5-HT in female sexual behavior......Page 355
5-HT 1A receptors......Page 356
5-HT 3 receptors......Page 358
Summary......Page 359
Implications for a role of 5-HT in male sexual behavior......Page 360
5-HT 1A receptors......Page 361
5-HT 1B receptors......Page 362
5-HT 2 receptors......Page 363
Measures of male sexual motivation......Page 364
Overall summary and future directions......Page 365
References......Page 366
Neuroanatomy of emotion......Page 373
Serotonergic innervation of the limbic system......Page 375
A gents that increase serotonergic neurotransmission......Page 376
A gents that decrease serotonergic neurotransmission......Page 378
Serotonin transporter gene polymorphism and emotional processing......Page 379
A gents acting directly on specific subtypes of serotonin receptor......Page 380
References......Page 381
A ims and scope of the chapter......Page 385
Operational definition of anxious states and anxiety-related behavior......Page 386
Models of anxious states with distinct temporal profiles......Page 387
Genetic models......Page 388
Adverse early life experience models......Page 389
Models of panic-like states......Page 390
The ventral hippocampus/subiculum as a nodal structure in anxiety-related circuits......Page 391
The dorsal periaqueductal gray as a nodal structure in mediating flight behavior......Page 392
Effects of serotonin within the basolateral amygdala......Page 393
Effects of serotonin within the ventral hippocampus/subiculum......Page 395
Summary and future directions......Page 396
References......Page 397
Introduction......Page 404
Effects of 5-HT on electrical self-stimulation of the LH and MFB......Page 405
5-HT and electrical self-stimulation of the hippocampus, MRN and DRN......Page 407
Place conditioning and effects of 5-HT......Page 408
Conditioned reward and 5-HT......Page 410
Delay of reward and 5-HT......Page 411
Involvement of 5-HT in regulation of alcohol drinking behavior in rodent models......Page 413
References......Page 416
Introduction......Page 420
Impulsivity in the five-choice serial reaction time task (5-CSRTT)......Page 421
Stop-signal reaction time task (SSRTT)......Page 423
Pharmacological fMRI......Page 424
Go/NoGo discrimination......Page 425
Temporal discounting of reward: impulsive choice......Page 426
5-HT and decision-making cognition......Page 427
Reversal learning and 5-HT......Page 428
Conclusions......Page 429
References......Page 430
Introduction......Page 433
Serotonin and adaptation of the gill withdrawal reflex in Aplysia californica......Page 434
Serotonin and learning in other invertebrates......Page 436
Inhibiting 5-HT reuptake......Page 437
Depleting 5-HT functions......Page 439
5,7-dihydroxytryptamine (5,7-DHT) lesions......Page 440
Concluding remarks......Page 441
Non-selective cholinergic lesions......Page 442
Selective cholinergic lesions......Page 443
Cholinergic drugs in combination with 5-HT depletion......Page 444
Reversing the effects of cholinergic drugs by acting on 5-HT 1A somatodendritic autoreceptors......Page 445
General conclusions......Page 446
References......Page 447
Serotonin and aggression......Page 452
Serotonin receptors and aggression......Page 453
Serotonin transporter and aggression......Page 454
MAOA and aggression......Page 455
TPH2 and aggression......Page 456
References......Page 457
Findings in animal models......Page 460
Mechanisms of 5-HT actions on nociception in the periphery......Page 462
Data from animal experiments......Page 463
Data from human studies......Page 466
5-HT in headache......Page 467
Fibromyalgia syndrome......Page 468
References......Page 469
Introduction......Page 475
Effects of stress on the raphe nuclei: c-Fos expression and neuronal firing......Page 476
Effect of stress on the synthesis of 5-HT......Page 478
Hippocampus, prefrontal cortex and amygdala......Page 479
Repeated and chronic stress......Page 483
Effects of stress on serotonergic neurotransmission in animal models of aberrant HPA axis functioning......Page 484
Concluding remarks and future......Page 485
References......Page 486
Introduction......Page 492
Serotonin in the etiology of depression......Page 493
Forced swim test (FST)......Page 494
Chronic mild stress (CMS)......Page 495
5-HT 1A receptor......Page 496
5-HT 2c receptor......Page 498
Conclusion......Page 499
References......Page 500
Introduction......Page 505
Measuring drug addiction in animal models......Page 506
The effects of cocaine on 5-HT activity......Page 507
Reducing and potentiating 5-HT activity......Page 508
5-HT 1A receptor......Page 510
5-HT 2A receptor......Page 513
5-HT 3 receptor......Page 514
Human studies......Page 515
The neurochemical effects of amphetamine on 5-HT......Page 516
5-HT 1A receptor......Page 517
5-HT 1B receptor......Page 518
The 5-HT system in amphetamine addiction......Page 519
5-HT 3 receptor......Page 520
Reducing and potentiating 5-HT activity......Page 521
5-HT 2B receptor......Page 522
The neurochemical effects of morphine and heroin on the 5-HT system......Page 523
Reducing and potentiating 5-HT activity......Page 524
Human studies......Page 525
The neurochemical effects of nicotine on the 5-HT system......Page 526
5-HT 4 and 5-HT 6 receptor......Page 527
Conclusion......Page 528
References......Page 529
Pharmacotherapy......Page 544
5-HTT binding studies at baseline......Page 546
Genetic association studies......Page 549
A nimal models......Page 552
Conclusion......Page 554
References......Page 555
Introduction......Page 561
5-HT synthesis......Page 562
5-HT breakdown......Page 563
5-HT transport and uptake......Page 565
Pre- and postsynaptic 5-HT receptors......Page 567
5-HT activity and functional associations......Page 568
5-HT activity and neurophysiological recording......Page 569
5-HT activity and neuroimaging......Page 570
References......Page 572
Introduction......Page 581
History of the serotonin hypothesis of schizophrenia......Page 582
The dopamine hypothesis of schizophrenia......Page 583
Effects of hallucinogens in human subjects......Page 584
Habituation......Page 586
5-HT 1A receptors......Page 587
5-HT 2A receptors......Page 588
Serotonin transporter (SERT)......Page 590
Genetic association studies regarding schizophrenia and serotonin......Page 591
5-HT 2A receptor antagonism......Page 593
Role of other 5-HT receptors......Page 595
A ntipsychotic drug action and serotonin receptor occupancy......Page 597
Serotonergic challenge studies......Page 598
Platelet studies......Page 599
Neurotrophic role of serotonin in the developmental disorder schizophrenia......Page 600
Serotonin – glutamate interactions......Page 601
Conclusions and future directions......Page 602
References......Page 603
Introduction......Page 617
Drug discrimination......Page 618
Prepulse inhibition of startle......Page 619
5-HT 1A receptor......Page 620
Chemistry and structure – activity relationships......Page 621
Receptors mediating the behavioral effects of MDMA in animals......Page 624
Locomotor activity......Page 625
Psilocybin......Page 626
Summary......Page 627
References......Page 628
Introduction......Page 633
Development of the cortical serotonergic innervation......Page 634
The barrel field as a model system for the study of serotonergic impact on morphogenesis......Page 635
V isual cortex......Page 637
Brief characterization of ASD......Page 638
Developmental neurobiology of ASD......Page 639
Evidence for serotonergic imbalances in ASD......Page 640
Experimental approaches to testing a serotonergic hypothesis of ASD......Page 641
Neuroinflammatory/neuroimmune interactions......Page 644
Environmental modulators......Page 645
A conceptual framework for the etiology of ASD behavioral endophenotypes......Page 646
References......Page 649
Introduction......Page 662
5-HT related drugs and the treatment of anxiety disorders......Page 663
A re anxiety disorders caused by disturbances in 5-HT-mediated neurotransmission?......Page 664
The dual role of 5-HT in anxiety: the Deakin and Graeff theory......Page 665
Experimental tests of the Deakin and Graeff theory: clinical studies......Page 667
Experimental tests of the Deakin and Graeff theory in laboratory animals: the elevated T-maze......Page 669
Genetic manipulations of the 5-HT system......Page 673
Conclusions......Page 674
References......Page 675
Introduction......Page 681
The emergence of the serotonin – aggression link......Page 684
Tryptophan depletion or supplementation and aggression......Page 685
Genetics of tryptophan hydroxylase and aggression......Page 686
5-HT 1 receptors and aggression......Page 687
Genetics of 5-HT 1 receptors and aggression......Page 689
Summary for 5-HT receptors and aggression......Page 690
Pharmacology of 5-HTT and aggression......Page 691
Summary for 5-HTT and aggression......Page 692
Genetics of MAOA and aggression......Page 693
Brain-derived neurotrophic factor (BDNF)......Page 694
General conclusions......Page 696
References......Page 697
Introduction......Page 708
Clinical symptoms and puzzling behaviors......Page 709
State and trait......Page 710
Investigations of serotonin metabolism......Page 711
Serotonin medication......Page 712
Imaging studies of 5-HT function......Page 713
Brain regions/pathways enervated by 5HT 1A/2A receptors......Page 714
5-HT transporter (5-HTT)......Page 715
Implications......Page 716
References......Page 717
Introduction......Page 723
Genetic, epigenetic and environmental effects that modulate serotonergic neurotransmission......Page 724
A ggression and impulsivity as behavioral manifestations of central serotonergic dysfunction......Page 726
Serotonergic neurotransmission and the response to acute alcohol intake......Page 727
Disposition to excessive alcohol intake: gene – environment interactions......Page 728
Serotonin and major depression......Page 731
Serotonin dysfunction and obsessive-compulsive disorder......Page 733
References......Page 734
Introduction......Page 741
Preclinical studies......Page 742
Human studies......Page 749
5-HT storage and release: vesicular monoamine transporter 2 (VMAT 2)......Page 750
Preclinical studies......Page 751
Human studies......Page 752
5-HT degradation: monoamine oxidase A (MAOA)......Page 753
Preclinical studies......Page 754
Preclinical studies......Page 760
Preclinical studies......Page 761
5-HT 2C receptor......Page 762
Human studies......Page 763
5-HT 4 receptor......Page 764
5-HT 6 receptor......Page 765
Summary and concluding remarks......Page 766
References......Page 767
Introduction......Page 782
5-HT 1A receptor......Page 783
Pharmacogenetics......Page 784
Genetic variability......Page 785
5-HT 2C receptor......Page 786
Pharmacogenetics......Page 787
Genetic variability and pharmacogenetics......Page 788
Genetic variability and pharmacogenetics......Page 789
5-HT 7 receptor......Page 790
Summary and synthesis......Page 791
References......Page 792
Index......Page 798