McArthur / Borsini | Animal and Translational Models for CNS Drug Discovery: Reward Deficit Disorders | E-Book | www.sack.de
E-Book

E-Book, Englisch, 432 Seiten, Web PDF

McArthur / Borsini Animal and Translational Models for CNS Drug Discovery: Reward Deficit Disorders


1. Auflage 2009
ISBN: 978-0-08-092040-5
Verlag: Elsevier Science & Techn.
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 432 Seiten, Web PDF

ISBN: 978-0-08-092040-5
Verlag: Elsevier Science & Techn.
Format: PDF
Kopierschutz: 1 - PDF Watermark



Reward Deficit Disorders is written for researchers in both academia and the pharmaceutical industry who use animal models in research and development of drugs for reward deficit disorders such as alcohol dependence, nicotine dependence, heroin and cocaine addiction, obesity, and gambling and impulse control disorders. Reward Deficit Disorders has introductory chapters expressing the view of the role and relevance of animal models for drug discovery and development for the treatment of psychiatric disorders from the perspective of (a) academic basic neuroscientific research, (b) applied pharmaceutical drug discovery and development, and (c) issues of clinical trial design and regulatory agencies limitations. Each volume examines the rationale, use, robustness and limitations of animal models in each therapeutic area covered and discuss the use of animal models for target identification and validation. The clinical relevance of animal models is discussed in terms of major limitations in cross-species comparisons, clinical trial design of drug candidates, and how clinical trial endpoints could be improved. Reward Deficit Disorders also has a section dedicated to the specifics of the regulatory aspects to abuse liability testing. The aim of this series of volumes on Animal and Translational Models for CNS Drug Discovery is to identify and provide common endpoints between species that can serve to inform both the clinic and the bench with the information needed to accelerate clinically-effective CNS drug discovery. This is the third volume in the three volume-set, Animal and Translational Models for CNS Drug Discovery 978-0-12-373861-5, which is also available for purchase individually. - Provides clinical, academic, government and industry perspectives fostering integrated communication between principle participants at all stages of the drug discovery process - Critical evaluation of animal and translational models improving transition from drug discovery and clinical development - Emphasizes what results mean to the overall drug discovery process - Explores issues in clinical trial design and conductance in each therapeutic area - Neurological Disorders is available for purchase individually.

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Weitere Infos & Material


1;Front Cover;1
2;Animal and Translational Models for CNS Drug Discovery;4
3;Copyright Page;5
4;Contents;8
5;Preface;16
6;Acknowledgements;40
7;List of Contributors;42
8;CHAPTER 1 Impulse and Reward Deficit Disorders: Drug Discovery and Development;44
8.1;Introduction;45
8.2;The Key Messages of Epidemiology: What should be Modeled?;45
8.2.1;Drug Addiction;46
8.2.2;Behavioral Addictions;46
8.3;Comorbid Associations;48
8.4;From Epidemiology to Unmet Medical Needs to Drug Discovery and Development;50
8.5;Challenges Facing Drug Discovery and Development in Impulse and Reward Deficit Disorders;51
8.6;Toward Translational Value of Animal Models in Impulse and Reward Deficit Disorders;53
8.6.1;Key Neurosystems Relevant to Drug Discovery and Development;53
8.6.2;Key Experimental Paradigms with Translational Potential for Drug Discovery and Development;54
8.6.3;Compulsive/Impulsive Behaviors;56
8.7;Target Validation and Throughput Limitations;57
8.8;Target Validation, Validity, Reliability, and Automation;58
8.9;Conclusions;58
8.10;References;59
9;CHAPTER 2 Drug Discovery and Development for Reward Disorders: Views from Government;66
9.1;Introduction and Contextual Issues;66
9.2;Division of Pharmacotherapies and Medical Consequences of Drug Abuse;67
9.2.1;Drug Discovery Program – Initial Operations;67
9.2.2;Drug Discovery Program – Current Status;69
9.2.3;Development of Medications for Opiate and Cocaine Addiction;70
9.3;Animal Models in the Discovery of Drug Addiction Treatments;73
9.3.1;The Validity of Animal Models in the Field of Drug Addiction;73
9.3.2;Use of Data from Animal Models for "Go/No Go" Decisions;73
9.3.3;Avoiding False Positives in Drug Self-administration and Relapse Model Testing;74
9.4;Translational Research, Human Laboratory Models, and the Bridge between Animal Models and Clinical Efficacy Trials;77
9.5;References;81
10;CHAPTER 3 Issues in Designing and Conducting Clinical Trials for Reward Disorders: A Clinical View;84
10.1;Introduction;84
10.2;Utility of Research using Animal Models;85
10.2.1;Advantages of Animal Research;85
10.2.2;Drug Exposure;85
10.2.3;Behavioral Techniques in Animal Research;86
10.2.4;Drug Self-administration;87
10.3;Human Testing Paradigms for New Medications;88
10.3.1;Human Laboratory;88
10.3.2;Self-administration;89
10.3.3;Neuroimaging;89
10.4;Methodological Issues in Clinical Trials;90
10.4.1;Target Population and Subject Selection;90
10.4.2;General Design Issues;92
10.4.3;Statistical Issues;94
10.5;Conclusions;95
10.6;Acknowledgments;96
10.7;References;96
11;CHAPTER 4 The Role of Animal Models in Reward Deficit Disorders: Views from Academia;102
11.1;Introduction and Definitions;103
11.2;Face and Construct Validity of Animal Models of Reward Deficits in Psychiatric Illness;104
11.3;Face Validity and Construct Validity of Animal Models of Reward Deficits in Psychiatric Disorders;105
11.3.1;Brain Stimulation Reward;105
11.3.2;Sucrose Consumption/Sucrose Preference;108
11.3.3;Progressive-Ratio Responding;108
11.4;Drug Withdrawal Model of Dependence;109
11.4.1;Brain Stimulation Reward As a Measure of the Reward Deficits Associated with Drug Dependence;110
11.4.2;Sucrose Intake/Preference As a Measure of the Reward Deficits Associated with Drug Dependence;110
11.4.3;Progressive-Ratio Responding As a Measure of Reward Deficits Associated with Drug Dependence;111
11.5;Chronic Mild Stress and Depression;113
11.5.1;Brain Stimulation Reward As a Measure of the Reward Deficits Associated with the Chronic Mild Stress Model of Depression;113
11.5.2;Sucrose Intake/Preference As a Measure of the Reward Deficits Associated with the Chronic Mild Stress Model of Depression;114
11.5.3;Progressive-Ratio Responding As a Measure of the Reward Deficits Associated with the Chronic Mild Stress Model of Depression;118
11.6;Validity of Animal Models of Reward Deficits;118
11.7;Common Neurobiological Substrates for the Reward Deficits in Addiction and Depression;119
11.7.1;Neurochemical Substrates in Dependence;119
11.7.2;Neurochemical Substrates in Depression;120
11.7.3;Extended Amygdala;121
11.7.4;Allostasis in Reward Function;122
11.8;Translational Value of these Models and Procedures for the Study of Reward Deficits in Man;123
11.9;Prospects for the Development of New Therapeutics of Reward Deficit Disorders;124
11.10;Summary and Conclusions;124
11.11;Acknowledgments;125
11.12;References;125
12;CHAPTER 5 Pharmacotherapy of Alcohol Dependence: Improving Translation from the Bench to the Clinic;134
12.1;Introduction;135
12.1.1;Epidemiology/Clinical and Societal Impact;135
12.1.2;Types of Alcoholism;137
12.1.3;Diagnostic Features of Alcohol Dependence;138
12.1.4;Clinical Diagnostic Criteria for Alcohol Dependence and Their Importance in the Development of Animal Models;139
12.1.5;Important Non-diagnostic Components of Alcohol Dependence;142
12.2;Current Treatment of Alcohol Dependence;145
12.3;Human Pharmacology and Experimental Medicine Approaches to the Treatment of Alcohol Dependence;150
12.3.1;Review of Clinical Trial Design;150
12.4;Behavioral Models of Alcohol Dependence;152
12.4.1;Voluntary Drinking Choice Model;152
12.4.2;Forced Alcohol Consumption;160
12.4.3;Effects of Clinically Effective and Novel Drugs on Alcohol Withdrawal;160
12.4.4;Alcohol Place Conditioning;161
12.4.5;Changes in Alcohol Place Conditioning After Chronic Treatment and Reinstatement of Conditioned Place Preference;163
12.4.6;Effects of Aversive Consequences on Alcohol Place Conditioning;163
12.4.7;Effects of Clinically Effective and Novel Drugs on Alcohol Place Conditioning;164
12.4.8;Family History of Alcohol Dependence;175
12.4.9;Genes Associated with Risk of Alcohol Dependence;177
12.5;Correspondence of Efficacy of Established and Novel Treatments for Alcohol Dependence in Animals and Humans;184
12.6;Consensus Statement Regarding Animal Models of Alcohol Dependence;185
12.7;References;187
13;CHAPTER 6 Contribution of Animal Models and Preclinical Human Studies to Medication: Development for Nicotine Dependence;222
13.1;Introduction;223
13.1.1;The Problem of Tobacco Smoking;223
13.1.2;Tobacco Addiction and Nicotine Dependence;223
13.1.3;Criteria for Defining Nicotine Dependence in Humans;227
13.2;Animal Models of Nicotine Dependence;228
13.2.1;What is a Model?;228
13.2.2;Models of Various Aspects of Nicotine Withdrawal;231
13.2.3;Models of Reinstatement of Nicotine-Seeking Behavior with Relevance to Relapse;232
13.2.4;Animal Models of Motivation for Nicotine;233
13.3;Historical Background: Why Drug Discovery on Nicotine Dependence Was Different from that on Other Drugs of Abuse;234
13.4;Preclinical Animal Models of Nicotine Dependence in Drug Discovery;236
13.4.1;Limitations of Drug Discovery Assays and Models for Nicotine Dependence;239
13.5;Human Preclinical and Clinical Studies;242
13.5.1;Ad Libitum Smoking Studies;243
13.5.2;Studies of Withdrawal Symptoms and "Craving" During Abstinence;244
13.5.3;Short-Term Abstinence Studies;245
13.5.4;Small-Scale Open-Label Studies;246
13.5.5;Commentary;246
13.6;Successes, Failures and Serendipity in Translational Research;247
13.7;Challenges, Opportunities, and Perspectives;248
13.7.1;Translational Medicine: From Mechanism of Action to Clinical Efficacy;248
13.7.2;Product Profile and Return-of-Research-Investment;249
13.7.3;Experimental Medicine Paradigm Shift and Translational Research;249
13.8;Acknowledgements;250
13.9;References;250
14;CHAPTER 7 Development of Medications for Heroin and Cocaine Addiction and Regulatory Aspects of Abuse Liability Testing;264
14.1;Introduction;265
14.1.1;Opioid and Cocaine Addiction;268
14.2;Pharmacotherapy for Drug Addiction and Abuse Potential of New Compounds;271
14.2.1;Animal Laboratory Models;271
14.2.2;Human Laboratory Models;280
14.3;Assessment of Abuse Liability of Compounds: the Regulatory Environment;285
14.3.1;Regulatory Environment in the United States and the EU;285
14.3.2;World Health Organization;287
14.4;Approved and Proposed Medications to Treat Opioid and Cocaine Addiction;288
14.4.1;Heroin (Opioid) Addiction;288
14.4.2;Cocaine Addiction;292
14.4.3;Concordance Between Animal and Human Laboratory Studies and Clinical Outcome;297
14.4.4;Improving the Predictive Value of Existing Models;298
14.4.5;Improving the Predictive Value of Existing Models in the Assessment of Abuse Liability;300
14.5;References;301
15;CHAPTER 8 Anti-obesity Drugs: From Animal Models to Clinical Efficacy;314
15.1;Introduction;315
15.2;Clinical Aspects of Obesity and Cardiometabolic Disease;316
15.2.1;Background – Do We Need Drugs for Obesity?;316
15.2.2;Current Drugs for Obesity and Their Limitations;317
15.2.3;Other Drugs – Withdrawn or No Longer Recommended for Routine Clinical Use;318
15.2.4;The Need for New Drugs;318
15.3;Biology and Genetics of Energy Regulation and Implications for Obesity;319
15.3.1;Short-Term (Episodic) Signals;319
15.3.2;Long-Term (Tonic) Signals;321
15.3.3;CNS Integrating Pathways;322
15.4;Biomarkers of Energy Regulation and Obesity;323
15.4.1;Anthropometric Measures;323
15.4.2;Measures of Adiposity;324
15.4.3;Measures of Energy Expenditure;324
15.4.4;Risk Factors;325
15.4.5;Insulin Resistance and Systemic Inflammation;325
15.5;The Psychobiology of Appetite Expression;326
15.5.1;Episodic Signals in the Regulation of Appetite Expression;326
15.5.2;Tonic Signals in the Regulation of Appetite Expression;326
15.6;Psychological and Behavioral Aspects of Obesity;326
15.6.1;Genetics Versus Environment?;327
15.6.2;Obese Eating Style?;327
15.6.3;Trait Hunger, Disinhibition, and Binge Eating;329
15.7;Behavioral Indices for Assessing the Action and Efficacy of Anti-obesity Drugs;330
15.7.1;Susceptibility to Obesity and Hyperphagia;330
15.7.2;Structure of Feeding Behavior;331
15.7.3;Assessing the Effects of Drugs on Human Feeding Behavior;331
15.7.4;Microstructure of Human Eating Behavior: Eating Rate, Cumulative Intake Curves and Deceleration;332
15.8;Molecular Targets for Anti-obesity Drugs;333
15.8.1;Lipase Inhibitors;333
15.8.2;Serotonin/Noradrenaline Reuptake Inhibitors;334
15.8.3;Selective Serotonin Receptor Ligands;335
15.8.4;Cannabinoid Receptor Ligands;338
15.8.5;Neuropeptide Receptor Ligands;338
15.9;Screening Strategies from Molecular Target to Initial Clinical Trial;340
15.10;Proof of Concept for Novel Anti-obesity Drugs: The Role of Experimental Medicine Studies to Determine Drug Efficacy and Side-effects;342
15.10.1;Measurement of Anti-Obesity Drug Efficacy in Experimental Medicine Studies: The UEM Approach;342
15.10.2;Measurement of Anti-Obesity Drug Efficacy and CNS Side-Effects in Experimental Medicine Studies: The Emotional Test Battery Approach;343
15.11;Summary;345
15.12;References;345
16;CHAPTER 9 Current Concepts in the Classification, Treatment and Modeling of Pathological Gambling and Other Impulse Control Disorders;360
16.1;Introduction;361
16.2;Neurobiology of Pathological Gambling;362
16.2.1;Biochemistry of Neurotransmitters;362
16.2.2;Stress Response Systems;365
16.2.3;Opioidergic Pathways;366
16.2.4;Neuroimaging;367
16.2.5;Genetic Considerations;368
16.2.6;Conclusions;369
16.3;Treatment;369
16.3.1;Pathological Gambling;369
16.3.2;Trichotillomania;374
16.3.3;Compulsive Buying/Shopping;376
16.3.4;Intermittent Explosive Disorder;377
16.3.5;Kleptomania;378
16.4;Insight from Animal Models;380
16.4.1;Animal Models of Gambling Behavior;380
16.4.2;The Feasibility of Modeling Gambling in Animals;381
16.4.3;Considerations for a Model of Pathological Gambling;383
16.4.4;Summary;385
16.5;Conclusions and Recommendations;385
16.6;References;386
17;EPILOGUE: Translational Models for the 21st Century: Reminiscence, Reflections and Some Recommendations;402
17.1;Introduction;402
17.2;References;412
18;Index;420
18.1;A;420
18.2;B;421
18.3;C;421
18.4;D;422
18.5;E;422
18.6;F;423
18.7;G;423
18.8;H;423
18.9;I;423
18.10;K;423
18.11;L;424
18.12;M;424
18.13;N;424
18.14;O;425
18.15;P;425
18.16;Q;425
18.17;R;426
18.18;S;426
18.19;T;426
18.20;U;426
18.21;V;426
18.22;W;426



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