The serotonin transporter is a key brain protein that modulates the reuptake of the neurotransmitter serotonin from synaptic spaces back into the presynaptic neuron. This control over neuronal signalling makes it a prime area of neuroscientific study. In this book an international team of top experts introduce and explicate the role of serotonin and the serotonin transporter in both human and animal brains. They demonstrate the relevance of the transporter and indeed the serotonergic system to substrates of neuropsychiatric disorders, and explain how this knowledge is translated into valid animal models that will help foster new discoveries in human neurobiology. Writing for graduate students and academic researchers, they provide a comprehensive coverage of a wide spectrum of data from animal experimentation to clinical psychiatry, creating the only book exclusively dedicated to this exciting new avenue of brain research.
Author(s): Allan V. Kalueff, Justin L. LaPorte
Edition: 1
Publisher: Cambridge University Press
Year: 2010
Language: English
Pages: 389
Cover......Page 1
Half-title......Page 3
Title......Page 5
Copyright......Page 6
Contents......Page 7
Contributors......Page 9
Preface: Focus on the serotonin transporter......Page 11
Abstract......Page 15
Introduction......Page 16
Serotonin transporter expression......Page 17
Extracellular serotonin levels......Page 23
Brain tissue serotonin levels......Page 35
Serotonin system architecture......Page 38
Conclusions......Page 43
References......Page 46
Abstract......Page 57
Introduction......Page 58
Developmental models......Page 59
Alterations in 5-HT receptors......Page 60
5-HT1A receptors......Page 61
5-HT2A receptors......Page 65
5-HT2C receptors......Page 66
5-HT3 receptors......Page 67
Impaired hypothalamic-pituitary-adrenal gland (HPA) axis......Page 68
Prenatal and maternal administration of SSRIs......Page 69
Adult models......Page 72
5-HT1A receptors......Page 73
Other 5-HT receptors......Page 76
Alterations in G-proteins and signal transduction pathways......Page 78
HPA axis......Page 79
Remarks and conclusions......Page 80
References......Page 81
Introduction......Page 92
Development of the serotonergic system......Page 93
Structural effects of 5-HT during embryogenesis in mammalian tissues......Page 95
Structural effects of 5-HT in the rodent somatosensory cortex......Page 98
Cellular mechanisms involved in developmental roles of 5-HT......Page 110
Potential relevance to human teratology......Page 114
References......Page 116
Abstract......Page 127
Introduction......Page 128
SERT mutant mice......Page 132
Anxiety......Page 134
Depression......Page 140
Limitations/future directions......Page 147
Summary......Page 150
References......Page 152
Introduction......Page 157
Animal models of depression......Page 160
Selective breeding......Page 162
Environmental manipulation during development......Page 163
Stress-related markers......Page 164
Sleep-related markers......Page 165
Biochemical markers in the central nervous system......Page 166
Behavior......Page 167
Biological markers......Page 168
Behavioral alterations in SERT mutants......Page 169
Tail suspension, forced swim tests, and anhedonia......Page 170
Shock avoidance, novelty suppressed feeding, and fear conditioning......Page 171
REMS and circadian rhythms......Page 172
Altered serotonergic system......Page 173
SERT heterozygous mutant mice......Page 175
Perspective: the developmental hypothesis of SERT dysfunction......Page 176
References......Page 180
Abstract......Page 192
The making of knock-out rats......Page 193
Confirmation of the SERT knock-out rat at the molecular level......Page 196
General appearance of SERT knock-out rats......Page 197
Presynaptic adaptations......Page 199
Locomotor activity......Page 204
5-HT1A receptor ligands......Page 205
Cocaine......Page 207
Anxiety and depression-related behavior......Page 211
Depression-related behavior......Page 212
Social play......Page 215
"Motor"
impulsivity......Page 217
Startle habituation, prepulse inhibition, spontaneous alteration, and Morris water maze......Page 219
Peripheral measurements......Page 220
Adaptive processes......Page 221
Rat vs. mouse......Page 222
Behavioral profile of SERT-/- rats......Page 223
SSRIs......Page 225
References......Page 226
Abstract......Page 236
Introduction......Page 237
Development of Wistar-Zagreb 5HT (WZ-5HT) sublines......Page 238
Peripheral 5HT......Page 242
Pharmacodynamic response......Page 244
Platelet aggregation and intracellular calcium......Page 245
Central 5HT......Page 246
5HT transporter analysis......Page 247
Metabolic enzymes......Page 248
Extraneuronal 5HT concentration......Page 250
5HT-receptors......Page 251
Behavioral responses......Page 252
Anxiety-related phenotype......Page 253
Depression-related phenotype......Page 255
Alcohol preference......Page 256
Concluding remarks......Page 257
References......Page 259
Abstract......Page 266
The role of SERT in cocaine reward......Page 267
Serotonin receptor subtypes......Page 270
Compensatory alterations in serotonin function in SERT KO mice......Page 274
Behavioral changes in SERT KO mice......Page 277
Rewarding effects of other addictive drugs......Page 280
Conclusions......Page 282
References......Page 283
Abstract......Page 292
Introduction......Page 293
Loss of BDNF single gene exacerbates 5-HT deficiencies in male SERT x BDNF (sb) double-mutant mice, but not in Female Mice......Page 295
Anxiety-like behaviors are gender-dependent in SERT x BDNF-deficient male, but not female, mice......Page 297
Targeting SERT- and BDNF-mediated brain disorders......Page 301
Acknowledgments......Page 303
References......Page 304
Abstract......Page 310
Introduction......Page 311
Associations between measures of serotonergic activity and behavioral traits of monkeys......Page 314
How manipulations of environmental experience can lead to altered serotonergic expression......Page 316
Associations between rh5-HTTLPR and behavioral traits in the rhesus macaque......Page 317
Gene-environment interactions involving rh5-HTTLPR......Page 318
Concluding remarks......Page 322
References......Page 323
Abstract......Page 330
Introduction......Page 331
Depression heritability......Page 334
Personality and depression-related traits......Page 336
Serotonin system in emotion regulation......Page 337
Serotonin transporter - bottleneck or master controller?......Page 338
Serotonin transporter in personality and disorders of emotion regulation......Page 342
Serotonin transporter, epigenetic interaction, and development: setting the stage for emotion regulation......Page 347
Variation of serotonin signaling and social organization in macaque species......Page 352
Imaging of emotionality: a risk assessment strategy for depression?......Page 354
Neural mechanisms of epigenetic processes: are social cognition and communication skills moderated by the serotonin transporter?......Page 358
Serotonin transporter deficient mouse: model for molecular and neural mechanisms of epigenetics?......Page 360
Future challenges......Page 363
References......Page 366
Index......Page 375
