Kendall / Alexander Behavioral Neurobiology of the Endocannabinoid System

1. Auflage 2009
ISBN: 978-3-540-88955-7
Verlag: Springer-Verlag
Format: PDF
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, 420 Seiten

Autoren/Hrsg.

Kendall, Dave

Alexander, Stephen

Inhaltsverzeichnis

1;Behavioral Neurobiology of the Endocannabinoid System;3
1.1;Preface;5
1.2;Contents;6
1.3;Biochemistry, Pharmacology, Genetics & Chemistry;12
1.3.1;The Life Cycle of the Endocannabinoids: Formation and Inactivation;13
1.3.1.1;Cannabinoid Signalling in the CNS;15
1.3.1.2;What Are Endocannabinoids?;15
1.3.1.3;Ester Endocannabinoids;16
1.3.1.3.1;Synthesis of Ester Endocannabinoids;16
1.3.1.3.1.1;Regulation of Phospholipase C Activity;19
1.3.1.3.1.2;Regulation of DGL Activity;19
1.3.1.3.1.3;Alternative Pathways of DAG and 2AG Synthesis;20
1.3.1.3.2;Hydrolysis of Ester Endocannabinoids;22
1.3.1.4;Amide Endocannabinoids;24
1.3.1.4.1;Synthesis of NAPEs;24
1.3.1.4.2;Synthesis of Amide Endocannabinoids;25
1.3.1.4.2.1;Pharmacological and Biochemical Manipulation of NAPE-PLD Activity;26
1.3.1.4.2.2;Alternative Pathways of Amide ECB Generation;28
1.3.1.4.3;Hydrolysis of Amide Endocannabinoids;30
1.3.1.4.3.1;FAAH1 Activity;30
1.3.1.4.3.2;FAAH2 Activity;31
1.3.1.4.3.3;NAAA Activity;32
1.3.1.5;Other Routes of ECB Transformation;32
1.3.1.5.1;Oxidative Metabolism of ECBs;33
1.3.1.5.1.1;Cyclooxygenase Activity;33
1.3.1.5.1.2;Lipoxygenase Activity;34
1.3.1.5.1.3;Cytochrome P450s and Epoxygenase Activity;34
1.3.1.6;Stimulation of ECB Synthesis and Release;35
1.3.1.7;Conclusion;37
1.3.1.8;References;37
1.3.2;Endocannabinoid Receptor Pharmacology;46
1.3.2.1;GPCR Overview;47
1.3.2.2;Receptor Pharmacology;48
1.3.2.2.1;GPCR Signaling;48
1.3.2.2.2;Radioligand Binding;49
1.3.2.2.3;GTPgammaS Binding as a Measure of GPCR Function;50
1.3.2.3;CB1 Receptor Gene Structure;53
1.3.2.3.1;Chromosomal Structure, Potential Alternative Splicing;53
1.3.2.3.2;CNR1 Polymorphisms;53
1.3.2.4;CB2 Receptor Gene Structure;54
1.3.2.4.1;CB2 Receptor Chromosomal Localization and Potential Alternative Splicing;54
1.3.2.4.2;CNR2 Polymorphisms;55
1.3.2.5;Structural Characteristics of the CB1 Receptor;55
1.3.2.6;Structural Characteristics of the CB2 Receptor;57
1.3.2.7;CB1 and CB2 Receptor Localization;58
1.3.2.8;Cellular Signaling of CB1 and CB2 Receptors;58
1.3.2.8.1;Inhibition of Adenylyl Cyclase - Gi/o Coupling of CB1 and CB2 Receptors;58
1.3.2.8.2;Cannabinoid Receptor Activation of MAP Kinases;59
1.3.2.8.3;Crosstalk Between Cannabinoid and Other Receptors;59
1.3.2.8.4;Transactivation Between Cannabinoid Receptors and Tyrosine Kinase Receptors;59
1.3.2.8.5;Cannabinoid Receptor-Mediated Modulation of Ion Channels;60
1.3.2.9;Implications of Constitutive Receptor Activity, Protean Agonism, and Inverse Agonism;60
1.3.2.10;Cannabinoid Receptor Ligands;62
1.3.2.10.1;Non-Selective CB1/CB2 Receptor Agonists;62
1.3.2.10.2;CB1 Receptor Antagonists;64
1.3.2.10.3;CB2 Receptor Agonists;64
1.3.2.10.4;CB2 Receptor Antagonists;65
1.3.2.10.5;Allosteric Modulators of Cannabinoid Receptors;65
1.3.2.11;Non-CB1/Non-CB2 Receptors;66
1.3.2.11.1;GPR55;66
1.3.2.11.2;Interactions of Cannabinoids with Ion Channels;66
1.3.2.12;Conclusions;67
1.3.2.13;References;67
1.3.3;Endocannabinoid Receptors: CNS Localization of the CB1 Cannabinoid Receptor;73
1.3.3.1;Introduction;74
1.3.3.2;Methodological Considerations for Localization Studies on the Endocannabinoid System;76
1.3.3.2.1;Negative Controls for Positive Findings;76
1.3.3.2.2;Positive Controls for Negative Findings;77
1.3.3.2.3;Quantification of Positive Findings;78
1.3.3.3;Regional Distribution;78
1.3.3.4;Cellular Distribution;82
1.3.3.5;Subcellular Distribution;84
1.3.3.6;Distribution of Other Molecular Components Involved in 2-AG Signaling;87
1.3.3.7;Conclusions;88
1.3.3.8;References;90
1.3.4;Pharmacological Tools in Endocannabinoid Neurobiology;95
1.3.4.1;Cannabinoid Receptor Ligands;96
1.3.4.2;Natural Products and Non-Selective Ligands;97
1.3.4.2.1;Classical Cannabinoids;98
1.3.4.2.2;Non-Classical Cannabinoids;98
1.3.4.2.3;Aminoalkylindoles;99
1.3.4.2.4;Eicosanoids;99
1.3.4.3;CB1-Selective Ligands;100
1.3.4.3.1;Agonists;100
1.3.4.3.2;Antagonists and Inverse Agonists;100
1.3.4.3.3;Allosteric Modulators;102
1.3.4.4;CB2-Selective Ligands;103
1.3.4.4.1;Agonists;103
1.3.4.4.2;Antagonists;104
1.3.4.5;Ligands of Other ECB Receptors;105
1.3.4.6;Modulators of ECB Metabolism;106
1.3.4.6.1;ECB Catabolism;106
1.3.4.6.1.1;Inhibition of Anandamide Transport;107
1.3.4.6.1.2;FAAH Inhibitors;108
1.3.4.6.1.3;MGL Inhibitors;110
1.3.4.6.1.4;NAAA Inhibitors;111
1.3.4.6.2;ECB Synthesis;112
1.3.4.7;References;113
1.3.5;Genetic Models of the Endocannabinoid System;119
1.3.5.1;Introduction;120
1.3.5.2;Genetic Models;122
1.3.5.2.1;Available Tools;122
1.3.5.2.2;Null Mutant Mouse Lines;128
1.3.5.2.3;Conditional CB1 Receptor Mutants;132
1.3.5.2.4;Complications with Cre Recombinase-Expressing Lines;136
1.3.5.3;Methodological Considerations on Behavioural Experiments with Mutant Mice;137
1.3.5.4;Caveats in Genetics and Pharmacology;139
1.3.5.5;Perspectives;141
1.3.5.6;References;141
1.3.6;Endocannabinoid Signaling in Neural Plasticity;148
1.3.6.1;Introduction;149
1.3.6.1.1;Definitions, Scope, Limitations, and Caveats;149
1.3.6.1.2;ECBs: Basic Principles;150
1.3.6.2;ECBs Regulate Synaptic Plasticity;151
1.3.6.2.1;Short-Term Plasticity;151
1.3.6.2.2;Short-Term Target-Dependent Plasticity;153
1.3.6.2.3;Long-Term Plasticity;153
1.3.6.2.3.1;Striatum;154
1.3.6.2.3.2;Nucleus Accumbens (NAc);155
1.3.6.2.3.3;Hippocampus;155
1.3.6.2.3.4;Cerebellum;156
1.3.6.2.3.5;Amygdala;157
1.3.6.2.3.6;Ventral Tegmental Area (VTA);157
1.3.6.2.3.7;Cortex;157
1.3.6.2.4;Mechanisms of ECB-Dependent Long-Term Plasticity;158
1.3.6.2.5;Sufficiency of CB1R Activation for ECB-LTD(or -iLTD) Induction;158
1.3.6.2.6;Molecular Mechanisms of ECB-LTD (or iLTD) Maintenance;160
1.3.6.2.7;Spike-Timing Dependent Plasticity (STDP);162
1.3.6.2.8;Interneurons Mobilize ECBs;164
1.3.6.3;Plasticity of the ECB System;165
1.3.6.3.1;Use-Dependence of CB1R Efficacy;165
1.3.6.3.2;Tonic CB1R Activation and ECB Regulation;166
1.3.6.3.3;Plasticity of ECB Mobilization;169
1.3.6.3.4;ECB Transport as a Synaptically Modifiable Process;170
1.3.6.3.5;The ECB System and Seizures;171
1.3.6.3.6;Interactions Between AEA and 2-AG;172
1.3.6.4;Conclusion;173
1.3.6.5;References;174
1.3.7;Lessons from Nonmammalian Species;180
1.3.7.1;Invertebrates;181
1.3.7.1.1;Insects;181
1.3.7.1.1.1;Ants;181
1.3.7.1.2;Aquatic Invertebrates and Annelids;183
1.3.7.1.2.1;Hydra (Hydra Vulgaris);183
1.3.7.1.2.2;Planaria;184
1.3.7.1.2.3;Leech;186
1.3.7.1.2.4;Snail;188
1.3.7.1.2.5;Sea Urchin;188
1.3.7.1.2.6;Urochordates Including the Sea Squirt (Ciona intestinalis);189
1.3.7.2;Nonmammalian Vertebrates;191
1.3.7.2.1;Fish;191
1.3.7.2.2;Amphibians;193
1.3.7.2.3;Birds;196
1.3.7.3;Lessons Learned;200
1.3.7.4;References;202
1.4; Physiology and Pathophysiology;206
1.4.1;Roles of the Endocannabinoid System in Learning and Memory;207
1.4.1.1;Introduction;208
1.4.1.2;Expression of Cannabinoid Receptors in the Brain: Focus on CB1;209
1.4.1.3;The ECS and Learning and Memory;210
1.4.1.4;Pharmacology of Exogenous Cannabinoid Agonists and Physiology of the ECS: Important Differences in Complex Functions;211
1.4.1.5;Involvement of the Endocannabinoid System in Learning and Memory;214
1.4.1.5.1;The ECS and Working Memory;214
1.4.1.5.2;The ECS and Long-Term Memories;216
1.4.1.5.2.1;The ECS and ``Declarative´´-Type Memories;216
1.4.1.5.2.2;The ECS and Recognition Memory;216
1.4.1.5.2.3;The ECS and Spatial Memory;217
1.4.1.5.3;The ECS and Procedural Memory;218
1.4.1.5.3.1;The ECS and Operant Conditioning;218
1.4.1.5.3.2;The ECS and Habits;219
1.4.1.5.3.3;The ECS and Procedural Strategies in a Spatial Task;220
1.4.1.5.4;The ECS and Emotional Memory;220
1.4.1.5.4.1;The ECS and Aversive Memory;220
1.4.1.5.4.2;The ECS and Fear Memory;221
1.4.1.5.4.2.1;Acquisition of Fear Memories;222
1.4.1.5.4.2.2;Consolidation, Re-consolidation and Extinction of Fear Memories;222
1.4.1.5.4.2.3;Intracellular Cascades;223
1.4.1.5.4.3;A Possible Mechanism for ECS-Dependent Extinction of Fear Memories in the Amygdala;224
1.4.1.6;General Conclusions;230
1.4.1.7;References;231
1.4.2;Endocannabinoids and the Non-Homeostatic Control of Appetite;237
1.4.2.1;Obesity and the Problem of Homeostasis;238
1.4.2.1.1;Eating for Survival;240
1.4.2.1.2;Gluttony and Externality;242
1.4.2.2;Endocannabinoids in Food Craving, Anticipation and Palatability;244
1.4.2.2.1;THC Hyperphagia;244
1.4.2.2.2;Orexigenic Actions of the Endocannabinoids;245
1.4.2.3;Behavioural Characterization of Cannabinoid Hyperphagia: The Reward Hypothesis;246
1.4.2.3.1;Endocannabinoids and ``Wanting´´: Primary Motivational Actions;248
1.4.2.3.2;Endocannabinoids and ``Liking´´: Secondary Motivational Actions;251
1.4.2.4;Endocannabinoid-Opioid Interactions in Eating Motivation;252
1.4.2.5;Endocannabinoids and Interactions with Other Orexigens;253
1.4.2.6;Conclusion;254
1.4.2.7;References;255
1.4.3;Cannabinoid/Endocannabinoid Signaling Impact on Early Pregnancy Events;260
1.4.3.1;Introduction;261
1.4.3.2;Endocannabinoid Systems;261
1.4.3.2.1;AEA Synthesis and Degradation;262
1.4.3.2.2;2AG Synthesis and Degradation;263
1.4.3.2.3;Cannabinoid Receptors;264
1.4.3.3;Peri-implantation Events;265
1.4.3.3.1;Preimplantation Embryo Development;266
1.4.3.3.2;Oviductal-Uterine Embryo Transport;268
1.4.3.3.3;Implantation;271
1.4.3.4;Conclusion;273
1.4.3.5;References;274
1.4.4;Targeting the Cannabinoid System to Produce Analgesia;279
1.4.4.1;Introduction;280
1.4.4.2;The Endogenous Cannabinoid System;281
1.4.4.2.1;Endocannabinoids;282
1.4.4.2.2;Endocannabinoid Synthesis;282
1.4.4.2.3;Endocannabinoid Metabolism;282
1.4.4.3;Endocannabinoids and Pain Processing;282
1.4.4.4;CB Receptor-Mediated Analgesia;283
1.4.4.5;Attenuation of Endocannabinoid Catabolism Produces Analgesia;284
1.4.4.6;Arthritis - A Therapeutic Target for Cannabinoids?;285
1.4.4.7;References;287
1.4.5;Integration of Endocannabinoid Signaling into the Neural Network Regulating Stress-Induced Activation of the Hypothal;292
1.4.5.1;Stress and the Hypothalamic-Pituitary-Adrenal Axis;293
1.4.5.2;The Endocannabinoid System;295
1.4.5.3;Endocannabinoid-Mediated Regulation of the HPA Axis;296
1.4.5.3.1;Endocannabinoid Signaling within the HPA Axis;296
1.4.5.3.2;Endocannabinoid Signaling Inhibits HPA Axis Activity;297
1.4.5.3.3;At What Sites of Action Does Endocannabinoid Signaling Modulate HPA Axis Activity?;298
1.4.5.4;Acute Stress-Induced Modulation of Endocannabinoid Signaling: Contributions to Glucocorticoid Negative Feedback;300
1.4.5.5;Chronic Stress-Induced Regulation of Endocannabinoid Signaling: A Driving Force for Stress Habituation;303
1.4.5.6;Conclusion;304
1.4.5.7;References;305
1.5;Pathology;310
1.5.1;Drug Addiction;311
1.5.1.1;Introduction;312
1.5.1.1.1;Drug Addiction;312
1.5.1.1.2;Endocannabinoid System in Brain Reward Circuitry;313
1.5.1.1.3;Release of Endocannabinoids by Abused Drugs;314
1.5.1.1.4;Endocannabinoids in Drug-Seeking and Relapse;315
1.5.1.2;Cannabinoids;316
1.5.1.2.1;Self-Administration of Cannabinoids;317
1.5.1.2.1.1;Drug Self-Administration Paradigm;317
1.5.1.2.1.2;Fixed-Ratio Schedule;318
1.5.1.2.1.3;Second-Order Schedule and Drug Seeking;322
1.5.1.2.2;Conditioned Place Preference and Aversion with Cannabinoids;324
1.5.1.2.2.1;THC and Synthetic Cannabinoids;324
1.5.1.2.2.2;AEA;325
1.5.1.2.3;Discriminative-Stimulus Effects of Cannabinoids;325
1.5.1.2.4;Tolerance, Physical Dependence and Behavioral Sensitization;327
1.5.1.2.4.1;Tolerance;327
1.5.1.2.4.2;Physical Dependence;328
1.5.1.2.4.3;Behavioral Sensitization;329
1.5.1.3;Opioids;330
1.5.1.4;Alcohol;331
1.5.1.5;Nicotine;332
1.5.1.6;Psychostimulants;333
1.5.1.6.1;Cocaine and Methylphenidate;334
1.5.1.6.1.1;Cocaine;334
1.5.1.6.1.2;Methylphenidate;335
1.5.1.6.2;Amphetamine, Methamphetamine and 3,4-Methylendioxymethamphetamine (MDMA);335
1.5.1.7;Endocannabinoid System and Treatment of Drug Addiction;336
1.5.1.8;References;337
1.5.2;Role of Endocannabinoid Signaling in Anxiety and Depression;349
1.5.2.1;Human Studies Suggesting a Role for Endocannabinoid Signaling in Anxiety;350
1.5.2.2;Animal Studies Indicating a Role for ECS in Anxiety;351
1.5.2.2.1;Effects of CB1 Receptor Blockade and Genetic Deletion on Unconditioned Anxiety Behaviors;351
1.5.2.2.2;Effects of Pharmacological and Genetic Augmentation of ECS on Unconditioned Anxiety Behaviors;353
1.5.2.2.3;Effects of CB1 Receptor Deletion and Pharmacological Blockade on Conditioned Anxiety Behaviors;354
1.5.2.2.4;Effects of ECS Augmentation on Conditioned Anxiety Behaviors;355
1.5.2.3;Neural Mechanisms Underlying Endocannabinoid Modulation of Anxiety;356
1.5.2.4;Human Studies Suggesting a Role for ECS in Depression;359
1.5.2.4.1;Cannabis Use and Depression;359
1.5.2.4.2;Depression and the ECS;360
1.5.2.5;Animal Studies Suggesting a Role for ECS in Depression;361
1.5.2.5.1;Evidence That Alteration of CB1 Receptor Signaling Results in Anti-Depressant-Like Effects;361
1.5.2.5.2;Evidence That Environmental Contexts That Produce Depression-Like Symptoms Alter ECS;363
1.5.2.5.3;Evidence That Anti-Depressant Therapies Alter ECS;364
1.5.2.6;Neural Mechanisms Underlying Endocannabinoid Modulation of Depression;364
1.5.2.7;Clinical Implications for Endocannabinoid-Based Therapeutics for Anxiety and Depressive Disorders;366
1.5.2.8;References;367
1.5.3;Feeding Disorders and Obesity;374
1.5.3.1;Introduction;375
1.5.3.2;Historical Background;376
1.5.3.3;Modes of Action by which Endocannabinoids Promote Energy Storage;376
1.5.3.3.1;Endocannabinoids Promote Energy Storage in the Brain;376
1.5.3.3.2;Endocannabinoids Promote Energy Storage at a Peripheral Level;377
1.5.3.3.2.1;Adipose Tissue;377
1.5.3.3.2.2;Liver;378
1.5.3.3.2.3;Skeletal Muscle;378
1.5.3.3.2.4;Endocrine Pancreas;378
1.5.3.4;Obesity as a Disease Model of Endocannabinoid Overactivation;379
1.5.3.5;Endocannabinoids and Central Eating Disorders;380
1.5.3.6;How CB1 Receptor Antagonism May Act Against Obesity and Metabolic Complications ;380
1.5.3.7;Pharmacological Implications in Humans;382
1.5.3.7.1;Rimonabant;382
1.5.3.7.2;Taranabant;383
1.5.3.8;Conclusions;383
1.5.3.9;References;384
1.5.4;Schizophrenia;387
1.5.4.1;Introduction;388
1.5.4.2;Neurobiology of the Endocannabinoid System in Schizophrenia;389
1.5.4.2.1;Animal Studies;389
1.5.4.2.2;Human Post-Mortem Studies;390
1.5.4.2.3;Clinical Studies;391
1.5.4.2.4;Cannabis Administration;392
1.5.4.3;Conclusions and Model;393
1.5.4.4;References;395
1.5.5;Tourette´s Syndrome;397
1.5.5.1;Tourette´s Syndrome;398
1.5.5.1.1;The Clinical Picture of Tourette´s Syndrome;398
1.5.5.1.2;The Aetiology of Tourette´s Syndrome;399
1.5.5.1.3;Treatment of Tourette´s Syndrome;399
1.5.5.1.4;Future Perspectives in the Treatment of Tourette´s Syndrome;400
1.5.5.2;Treatment of Tourette´s Syndrome with Cannabinoids;400
1.5.5.2.1;Anecdotal Reports;400
1.5.5.2.2;Uncontrolled Single Case Studies;401
1.5.5.2.3;Controlled Single-Dose Trial;402
1.5.5.2.4;Six-Week Randomized Trial;403
1.5.5.3;Adverse Effects;404
1.5.5.4;Central Cannabinoid Receptor (CNR1) Gene in Tourette´s Syndrome;405
1.5.5.5;In Vivo Imaging of Central Cannabinoid CB1 Receptors in TS Using [123I]AM281 and SPECT;405
1.5.5.6;Possible Explanations for Beneficial Effects of Cannabinoids in TS;405
1.5.5.7;Conclusions and Perspective;407
1.5.5.8;References;408
1.6;Index;411