Handbook of Experimental Pharmacology

By: Gaetano Di Chiara, Michael Stix

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Hardcover | 27 June 2002

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540 Pages

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Dopamine was initially regarded as a mere precursor of noradrenaline, but has progressively gained its present status of a common target for major drug classes and a substrate for some basic functions and dysfunctions of the Central Nervous System. The scientific interest has shifted from typically motor areas of the striatum to traditionally limbic ones as the nucleus accumbens and its afferent areas, the prefrontal cortex, the hippocampal formation and the basolateral amygdala. This double volume provides a systematic account of the anatomy, physiology, neurochemistry, molecular biology and behavioural pharmacology of dopamine in the CNS. The second volume deals with functional and behavioural aspects as the electrophysiology of dopamine neurons and of dopamine actions, the interaction with other transmitters and its role in behaviour and in the action of centrally acting drugs.

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Non-Fiction Science Biology, Life Sciences Biochemistry Medicine Clinical & Internal Medicine Neurology & Clinical Neurophysiology Nursing & Ancillary Services Pharmacy & Dispensing Other Branches of Medicine Pharmacology Molecular Biology

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Electrophysiological Pharmacology of Mesencephalic Dopaminergic Neurons	p. 1
Introduction	p. 1
Anatomical Organization	p. 2
Basic Electrophysiological Properties	p. 4
Extracellular Recordings	p. 4
Intracellular Recordings	p. 7
Afferents to Dopaminergic Neurons	p. 8
GABAergic Afferents	p. 8
Glutamatergic Afferents	p. 14
Cholinergic Afferents	p. 19
Monoaminergic Afferents	p. 20
Autoreceptor-Mediated Effects on Dopaminergic Neurons	p. 22
Somatodendritic Autoreceptors	p. 22
Axon Terminal Autoreceptors	p. 24
Are D(2) Autoreceptors Different from Other D(2) Receptors?	p. 25
Are Autoreceptors Ubiquitous Among Dopaminergic Neurons?	p. 26
What Are the Physiological Roles of Autoreceptors?	p. 28
Miscellaneous Neuropharmacology	p. 31
Gamma-Hydroxybutyric Acid	p. 31
Glycine	p. 31
Neuropeptides	p. 31
Acute and Chronic Effects of Antipsychotics on Dopaminergic Neurons	p. 33
Differences Between Effects of Typical and Atypical Antipsychotics	p. 33
Effects of Chronic Antipsychotic Drug Administration -The Depolarization Block Hypothesis	p. 34
Dopaminergic Neurons and Drugs of Abuse: Acute and Chronic Studies	p. 36
Acute Effects of Drugs of Abuse on Dopaminergic Neurons	p. 36
Chronic Effects of Drugs of Abuse on Dopaminergic Neurons	p. 38
Withdrawal Following Chronic Administration	p. 40
Conclusions	p. 42
References	p. 43
Presynaptic Regulation of Dopamine Release	p. 63
Introduction	p. 63
Interactions Between Heteroreceptors or Heteroreceptors and D(2) Autoreceptors Present on Dopaminergic Nerve Terminals	p. 64
Role of Diffusible Messengers in the Presynaptic Control of Striatal Dopaminergic Transmission	p. 67
Local Circuits Involved in the Control of DA Transmission in Striatal Compartments	p. 70
Similarities and Differences in the Presynaptic Regulation of DA Release in Striatal Compartments	p. 72
The GABA- and Dynorphin-Dependent Inhibitions of DA Transmission Triggered by Acetylcholine Occur in Two Distinct Matrix Territories	p. 73
NMDA-Dependent Local Inhibitory Circuits of DA Transmission Occur in Both Striatal Compartments and Involve Gabaand Dynorphin	p. 74
Facilitation by DA of the NMDA-Sensitive Local Inhibitory Circuits Involved in the Presynaptic Regulation of DA Release in Striatal Compartments	p. 74
Conclusions	p. 78
References	p. 78
Dopamine - Acetylcholine Interactions	p. 85
Introduction	p. 85
Dopamine - Acetylcholine Interactions in the Basal Ganglia	p. 85
Early Studies	p. 86
Direct D(1) Receptor-Mediated Facilitation of Striatal Acetylcholine Transmission	p. 89
Separate Transduction Pathways for D(1) and D(2) Receptor-Mediated Influences on AcetylcholineTransmission	p. 92
Independent Gating of Input to Striatal Acetylcholine Neurons by Dopamine Receptor Subtypes	p. 92
Relative Role of D(1) and D(2) Receptors in the Control of Striatal Acetylcholine Function	p. 95
Nicotinic Receptors and Dopamine Neurons	p. 98
Actions of Nicotine on Dopamine Function	p. 98
Mechanism of Nicotine Actions on Dopamine Function	p. 100
Dopamine - Acetylcholine Interactions Outside the Basal Ganglia	p. 103
Dopaminergic Regulation of Cortical and Hippocampal Acetylcholine Transmission	p. 104
References	p. 105
Dopamine - Glutamate Interactions	p. 117
Introduction	p. 117
Neuropharmacological Interactions	p. 117
Dopamine and Glutamate Act Within the Same Neuronal Circuits	p. 117
Dopamine and Glutamate Receptors in the Striatum	p. 118
Reciprocal Release Regulation of Dopamine and Glutamate by Dopamine Receptors and IonotropicGlutamate Receptors	p. 119
Reciprocal Regulation of Receptor Synthesis	p. 120
Glutamate Regulates the Synthesis of Dopamine in Striatal Synaptosomes	p. 120
Glutamate and Dopamine Are Co-released from Dopamine Neurons	p. 121
Intraneuronal Interactions	p. 121
Dopamine Receptors and NMDA Receptors Cooperatively Modulate Gene Expression	p. 121
Electrophysiological Interactions	p. 122
Striatal Organization	p. 122
Dopamine Modulates Glutamate Inputs	p. 124
Interaction of the Dopamine and Glutamate Neurotransmitter Systems in Other Brain Areas	p. 126
Functional Consequences of the Interaction of the Glutamate and Dopamine Systems	p. 127
References	p. 128
Dopamine - Adenosine Interactions	p. 135
Adenosine in the CNS	p. 135
Receptor Distribution	p. 135
Adenosine in CNS Pathology	p. 137
Pharmacology of Adenosine Receptors	p. 138
Adenosine - Dopamine Interactions	p. 139
Dopamine D(1) and Adenosine Receptors	p. 140
Dopamine D(2) and Adenosine Receptors	p. 141
Modulation of Dopamine Release	p. 143
Therapeutic Implications	p. 144
References	p. 145
Dopamine - GabaInteractions	p. 151
Introduction	p. 151
The Anatomical Relationship Between Nigrostriatal Dopamine and GabAergic Neurons	p. 151
Substantia Nigra	p. 151
Striatum	p. 152
Other Basal Ganglia Regions	p. 152
Functional Interactions Between Gabaand Nigrostriatal Dopaminergic Neurons	p. 153
Striatum	p. 153
Effects of Gabaon Dopaminergic Neurons	p. 153
Effects of Dopamine on GABAergic Output Neurons	p. 153
Dopaminergic Regulation of Striatal GABAergic Interneurons	p. 155
Dopaminergic Regulation of Striatal GabaRelease	p. 155
Dopamine - GabaInteractions in the Globus Pallidus	p. 156
Gaba- DA Interactions in the Internal Pallidum	p. 158
DA - GabaInteractions in the Substantia Nigra	p. 159
Functional Implications of Gaba- DA Interactions Within the Basal Ganglia	p. 160
DA - GabaInteractions in the Mesolimbic Pathway	p. 161
DA - GabaInteractions in the Mesocortical System	p. 163
References	p. 165
Dopamine - Its Role in Behaviour and Cognition in Experimental Animals and Humans	p. 173
Introduction	p. 173
Electrophysiological and Neurocomputational Approaches	p. 174
Neuropharmacological Evidence for a Role for Dopamine in Learning	p. 176
Overview of Results from In Vivo Monitoring Studies	p. 176
Psychopharmacological Evidence of Specific Actions of Dopamine on Learning and Memory	p. 178
The Possible Complication of a Role for Dopamine in Attentional Function	p. 182
Models of ADHD	p. 185
Working Memory	p. 186
Problems of Interpretation of the Role of the PFC in Working Memory	p. 190
Evidence for a Role for Dopamine in Cognition in Humans	p. 192
Dopamine and Cognition in Clinical Disorders: Parkinson's Disease, Schizophrenia, Acute Brain Injury and ADHD	p. 193
Effects of Dopaminergic Drugs on Cognition in Normal Human Volunteers	p. 196
Conclusions and Future Directions	p. 199
References	p. 203
Molecular Knockout Approach to the Study of Brain Dopamine Function	p. 213
Introduction	p. 213
Limitations of the Knockout Approach: Compensation and Epistasis	p. 216
Overview of the Midbrain Dopamine System in Motor Behavior and Reward	p. 218
Overview of the Dopamine Receptor Subtypes in Motor Behavior and Reward	p. 219
D(1) Receptor Knockouts	p. 220
D(2) Receptor Knockouts	p. 222
D(3) Receptor Knockouts	p. 224
Knockout of the Dopamine Transporter	p. 225
Knockout of Tyrosine Hydroxylase Gene	p. 227
Other Knockouts	p. 229
Summary and Conclusions: What We Know That We Did Not Know Before Knockouts	p. 231
References	p. 232
Behavioural Pharmacology of Dopamine D(2) and D(3) Receptors: Use of the Knock-out Mice Approach	p. 239
Introduction	p. 239
Behavioural Pharmacology of DA D(2)/D(3) Receptor Agonists	p. 240
Correlational Studies Using DA D(2)/D(3) Receptor Agonists	p. 241
Behavioural Pharmacology of DA D(2)/D(3) Receptor Antagonists	p. 242
Dopamine D(3) Receptor Knock-out Mice	p. 245
Analysis of the Phenotype of D(3) Receptor Knock-out Mice	p. 246
Effects of DA Receptor Ligands in D(3) Receptor Knock-out Mice	p. 246
DA D(2)/D(3) Receptor Agonists	p. 247
DA D(2)/D(3) Receptor Antagonists	p. 247
Psychostimulants	p. 247
Dopamine D(2) Receptor Knock-out Mice	p. 247
Analysis of the Phenotype of D(2) Receptor Knock-out Mice	p. 248
Effects of DA Receptor Ligands in D(2) Receptor Knock-out Mice	p. 248
DA D(2)/D(3) Receptor Agonists	p. 249
DA D(2)/D(3) Receptor Antagonists	p. 249
Psychotropic Agents	p. 249
Direct Comparison Between D(2) and D(3) Receptor Knock-out Mice	p. 250
Comparison of Avoidance Behaviour of D(2) and D(3) Receptor Knock-out Mice	p. 251
Comparison of Effects of DA Receptor Ligands in D(2) and D(3) Receptor Knock-out Mice	p. 252
Psychotropic Agents	p. 252
DA Receptor Antagonists	p. 255
Conclusions	p. 256
References	p. 257
Dopamine and Reward	p. 265
Introduction	p. 265
Terminology	p. 266
Reward, Reinforcer, Incentive	p. 267
Motivation and Instrumental Responding	p. 268
Incentive-Motivational Responding	p. 269
Instrumental Responding	p. 270
Early Studies: The Original and the Revised Anhedonia Hypothesis	p. 272
Testing the Original Anhedonia Hypothesis	p. 274
Sweet Reward	p. 274
Operant Responding for Sweet Reward	p. 280
The Motor Deficit Issue	p. 281
Response-Reinforcement Functions	p. 285
Reward Summation Studies	p. 285
Intensity-Threshold Studies	p. 286
Response-Reinforcement Matching Studies	p. 287
Dissociating Reinforcement from Incentive-Motivation and Performance	p. 289
Incentive Accounts of the Role of Dopamine in Behaviour	p. 291
Stimulus-Bound Incentive Role of Dopamine?	p. 293
Dopamine and Incentive Arousal	p. 294
Incentive Role of Drug-Stimulated Dopamine Transmission	p. 295
Associative Learning Accounts	p. 296
Pavlovian Incentive Learning	p. 296
Place-Conditioning Studies	p. 301
An Interpretative Framework of the Role of Dopamine in Reward	p. 304
References	p. 309
Molecular and Cellular Events Regulating Dopamine Neuron Survival	p. 321
Introduction	p. 321
Mechanisms of DA Cell Death	p. 322
Extraneuronal Events	p. 323
Noradrenergic System	p. 323
NE in Experimental Parkinsonism	p. 325
Excitatory Amino Acids	p. 327
Excitotoxicity in PD	p. 327
Excitotoxicity in Experimental Parkinsonism	p. 329
The MPTP Model	p. 329
Species Differences in MPTP Toxicity	p. 331
MPP(+) Kinetics	p. 332
Excitotoxicity in the MPTP Model	p. 335
Methamphetamine Toxicity	p. 336
6-OHDA Toxicity	p. 337
Conclusions on Excitotoxicity	p. 339
Neurotrophic Factors	p. 340
Intraneuronal Events	p. 343
Oxidative Stress	p. 343
Nitric Oxide	p. 345
Apoptosis and Mitochondria	p. 346
Cytochrome P450 System	p. 347
Cytochrome P450 in the CNS	p. 348
P450 System and DA Neurons	p. 349
CYP 2D6	p. 350
CYP 2E1	p. 351
The P450 System in PD	p. 351
P450 in Experimental Parkinsonism	p. 353
Toxicity of Dopamine	p. 355
DA and Apoptosis	p. 358
Conclusions About the Pathogenesis of PD	p. 359
References	p. 362
Dopamine and Depression	p. 387
Introduction	p. 387
DA Function in Affective Disorders	p. 389
DA Turnover	p. 389
DA Receptors	p. 391
Neuroendocrine Studies	p. 392
Summary	p. 393
Mood Effects of DA Agonists and Antagonists	p. 393
Psychostimulants	p. 393
DA-Active Antidepressants	p. 394
Neuroleptic-Induced Depression	p. 396
Parkinson's Disease	p. 397
Neuroleptics as Antidepressants	p. 397
Summary	p. 399
Dopaminergic Consequences of Antidepressant Treatment	p. 399
DA autoreceptor Desensitization	p. 399
Sensitization of D(2)/D(3) Receptors	p. 400
Clinical Evidence	p. 401
Summary	p. 402
Dopaminergic Mechanisms in Animal Models of Depression	p. 402
D(2)/D(3) Receptor Sensitization as a Mechanism of Antidepressant Action	p. 402
Clinical Evidence	p. 404
Reciprocal Changes in DA Responses to Reward and Stress	p. 404
Summary	p. 405
Conclusions	p. 406
Limitations of the Dopamine Hypothesis	p. 406
Syndromes or Symptoms?	p. 407
The Wider Picture	p. 408
References	p. 409
Dopamine in Schizophrenia Dysfunctional Information Processing in Basal Ganglia -Thalamocortical Split Circuits	p. 417
The Dopamine Hypothesis of Schizophrenia	p. 417
Schizophrenia as a Dopamine-Dependent Dysfunctional Information Processing in Basal Ganglia - Thalamocortical Circuits	p. 423
Circuit Models of Schizophrenia	p. 425
The Split Circuit Model of Schizophrenia	p. 428
Striatum as a Contention Scheduling Device	p. 430
The Interaction Between the Striatum and the Frontal Cortex	p. 432
Contention Scheduling of Goals by the Limbic Striatum	p. 433
The Role of Tonic and Phasic DA in the Contention Scheduling of Goals	p. 433
Tonic and Phasic DA Release	p. 434
The Establishment of Goals in the Limbic Striatum	p. 436
Goal Selection	p. 436
Goal Maintenance and Energizing	p. 437
Switching Between Goals	p. 438
The Translation of Goals to Behavior	p. 439
Schizophrenia	p. 440
Fronto-temporo-limbic Cortical Dysfunction and Dysregulation of Tonic and Phasic DA Transmission in Schizophrenia	p. 442
The Consequences of Fronto-temporo-limbic Cortical Dysfunction: Disrupted Establishment of Goals	p. 442
The Consequences of Dysregulation of the DA Input to the Limbic Striatum	p. 444
Reduced Tonic DA: Goal Selection, Activation and Maintenance	p. 444
Abnormal Phasic DA Release: Learning and Switching	p. 446
Summary: Phasic and Tonic DA Dysregulation and Schizophrenia Symptoms	p. 449
References	p. 451
Atypical Antipsychotics	p. 473
Introduction	p. 473
Receptor Binding Profile of Antipsychotics	p. 474
Interaction with Dopamine Receptors	p. 481
Interaction with 5-HT(2) and Other 5-HT Receptors	p. 483
Interaction with Various Biogenic Amine Receptors	p. 484
Future Antipsychotics	p. 485
Conclusions	p. 486
Abbreviations	p. 487
References	p. 487
Sleep and Wake Cycle	p. 491
Introduction	p. 491
Dopaminergic Action in Sleep	p. 492
D(2) Antagonists	p. 492
D(2) Agonists	p. 493
D(1) Antagonists	p. 494
D(1) Agonists	p. 494
More Specific Studies	p. 494
Catecholaminergic Pathway Modulation	p. 495
Temperature Regulation	p. 495
Pharmacological Interactions	p. 496
Serotonin	p. 496
Adrenergic System	p. 497
Acetylcholine	p. 498
Histamine	p. 498
H(1) Receptor	p. 499
H(2) Receptor	p. 499
H(3) Receptor	p. 499
GABAergic System	p. 499
Summary	p. 500
References	p. 501
Subject Index	p. 507
Table of Contents provided by Publisher. All Rights Reserved.

Handbook of Experimental Pharmacology

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