راهنمای نوروبیولوژی رفتاری سروتونین (جلد ۲۱) (راهنمای علوم اعصاب رفتاری، جلد ۲۱)

Serotonin (5-hydroxytryptamine, often cited as 5-HT) is one of the major excitatory neurotransmitter, and the serotonergic system is one of the best studied and understood transmitter systems. It is crucially involved in the organization of virtually all behaviours and in the regulation of emotion and mood. Alterations in the serotonergic system, induced by e.g. learning or pathological processes, underlie behavioural plasticity and changes in mood, which can finally results in abnormal behaviour and psychiatric conditions. Not surprisingly, the serotonergic system and its functional components appear to be targets for a multitude of pharmacological treatments - examples of very successful drugs targeting the serotoninergic system include Prozac and Zoloft. The last decades of research have not only fundamentally expanded our view on serotonin but also revealed in much more detail an astonishing complexity of this system, which comprises a multitude of receptors and signalling pathways. A detailed view on its role in basal, but also complex, behaviours emerged, and, was presented in a number of single review articles. Although much is known now, the serotonergic system is still a fast growing field of research contributing to our present understanding of the brains function during normal and disturbed behaviour. This handbook aims towards a detailed and comprehensive overview over the many facets of behavioural serotonin research. As such, it will provide the most up to date and thorough reading concerning the serotonergic systems control of behaviour and mood in animals and humans. The goal is to create a systematic overview and first hand reference that can be used by students and scholars alike in the fields of genetics, anatomy, pharmacology, physiology, behavioural neuroscience, pathology, and psychiatry. The chapters in this book will be written by leading scientists in this field. Most of them have already written excellent reviews in their field of expertise. The book is divided in 4 sections. After an historical introduction, illustrating the growth of ideas about serotonin function in behaviour of the last forty years, section A will focus on the functional anatomy of the serotonergic system. Section B provides a review of the neurophysiology of the serotonergic system and its single components. In section C the involvement of serotonin in behavioural organization will be discussed in great detail, while section D deals with the role of serotonin in behavioural pathologies and psychiatric disorders. * The first handbook broadly discussing the behavioral neurobiology of the serotonorgic transmitter system * Co-edited by one of the pioneers and opinion leaders of the past decades, Barry Jacobs (Princeton), with an international list (10 countries) of highly regarded contributors providing over 50 chapters, and including the leaders in the field in number of articles and citations: K. P. Lesch, T. Sharp, A. Caspi, P. Blier, G.K. Aghajanian, E. C. Azmitia, and others * The only integrated and complete resource on the market containing the best information integrating international research, providing a global perspective to an international community. * Of great value not only for researchers and experts, but also for students and clinicians as a background reference. 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