In vivo Models for Drug Discovery E-Book

• Herausgeber: Wiley-VCH
• Kategorie: Wissenschaft und neue Technologien
• Serie: Methods and Principles in Medicinal Chemistry
• Sprache: Englisch

Seitenzahl: 1239

Veröffentlichungsjahr: 2014

Beschreibung

This one-stop reference is the first to present the complete picture -- covering all relevant organisms, from single cells to mammals, as well as all major disease areas, including neurological disorders, cancer and infectious diseases. Addressing the needs of the pharmaceutical industry, this unique handbook adopts a broad perspective on the use of animals in the early part of the drug development process, including regulatory rules and limitations, as well as numerous examples from real-life drug development projects. After a general introduction to the topic, the expert contributors from research-driven pharmaceutical companies discuss the basic considerations of using animal models, including ethical issues. The main part of the book systematically surveys the most important disease areas for current drug development, from cardiovascular to endocrine disorders, and from infectious to neurological diseases. For each area, the availability of animal models for target validation, hit finding and lead profiling is reviewed, backed by numerous examples of both successes and failures among the use of animal models. The whole is rounded off with a discussion of perspectives and challenges. Key knowledge for drug researchers in industry as well as academia.

Leseprobe

CONTENTS

Cover

Methods and Principles in Medicinal Chemistry

Title Page

Copyright

List of Contributors

Preface

A Personal Foreword

Part I: Transversal Issues Concerning Animal Models in Drug Discovery

Chapter 1: The 3Ns of Preclinical Animal Models in Biomedical Research

1.1 First N: The Need for Use of Animal Models

1.2 Second N: The Need for Better Animal Models

1.3 Third N: The Need for 3Rs Guiding Principles

References

Chapter 2: Alternative Models in Drug Discovery and Development Part I: In Silico and In Vitro Models

2.1 Introduction

2.2 In Silico Models

2.3 In Vitro Models

References

Chapter 3: Alternative Models in Drug Discovery and Development Part II: In Vivo Nonmammalian and Exploratory/Experimental Human Models

3.1 Introduction

3.2 In Vivo Nonmammalian Models

3.3 In Vivo Exploratory and Experimental Human Models

References

Chapter 4: Ethical Issues and Regulations and Guidelines Concerning Animal Research

4.1 Introduction

4.2 Current Use of Animals in Biomedical and Pharmaceutical Research

4.3 Ethical Concerns and Positions on Animal Research

4.4 General Principles for the Ethical Use of Animals in Research

4.5 Regulatory Framework for Use of Animals in Research

Acknowledgment

References

Chapter 5: Regulatory Issues: Safety and Toxicology Assessment

5.1 Introduction

5.2 Animal Species in Toxicology Studies

5.3 Toxicology Studies

5.4 Translation to Clinics: Limitations and Difficulties

References

Chapter 6: Generation and Use of Transgenic Mice in Drug Discovery

6.1 Introduction

6.2 Improved Mouse Genetic Engineering

6.3 Functional Evaluation and Uses of Mouse Models

6.4 Translation to Clinics: Limitations and Difficulties

6.5 Perspectives

Acknowledgments

References

Chapter 7: In Vivo Brain Imaging in Animal Models: A Focus on PET and MRI

7.1 Introduction: Role of Animal in In Vivo Imaging

7.2 The Choice of the Right Imaging Modality for Brain Imaging

7.3 Small Animal Magnetic Resonance Imaging

7.4 Positron Emission Tomography

7.5 Clinical Translation: Limitations and Difficulties

References

Part II: Animal Models in Specific Disease Areas of Drug Discovery

Chapter 8: Substance Abuse and Dependence

8.1 Introduction

8.2 Difficulties to Model Addiction in Animals

8.3 Tolerance, Sensitization, and Physical Withdrawal

8.4 Reward and Reinforcement

8.5 Translation to Clinics: Limitations and Difficulties

References

Chapter 9: Mood and Anxiety Disorders

9.1 Introduction

9.2 Animal Models of Anxiety Disorders

9.3 Animal Models of Mood Disorders

9.4 Translation to Clinics: Limitations and Difficulties

Acknowledgment

References

Chapter 10: Schizophrenia

10.1 Introduction

10.2 Models Amenable to Use in Screening

10.3 Translation to the Clinic: Limitations and Difficulties

References

Chapter 11: Migraine and Other Headaches

11.1 Introduction

11.2 Vascular Models

11.3 Neurogenic Inflammation

11.4 Nociceptive Activation of the Trigeminovascular System

11.5 Cortical Spreading Depression

11.6 Human Experimental Migraine Provoking Models

11.7 Animal Experimental Migraine Provoking Models

11.8 Transgenic Models

11.9 Behavioral Models

11.10 Translation to Clinics: Limitations and Difficulties

References

Chapter 12: Nociceptive, Visceral, and Cancer Pain

12.1 Introduction

12.2 Acute Pain Tests

12.3 Visceral Pain Models

12.4 Cancer Pain Models

12.5 Translation to Clinics: Difficulties and Limitations

References

Chapter 13: Inflammatory, Musculoskeletal/Joint (OA and RA), and Postoperative Pain

13.1 Introduction: Evaluation of Pain in Animal Models

13.2 Inflammatory Pain

13.3 Musculoskeletal/Joint Osteoarthritis (OA) and Rheumatoid Arthritis (RA) Pain

13.4 Postoperative Pain

13.5 Translation to Clinics: Limitations and Difficulties

References

Chapter 14: Neuropathic Pain

14.1 Introduction

14.2 Main Types of Neuropathic Pain in Humans

14.3 Modelization of Chronic Pain in Rodents

14.4 Translation to Clinics: Limitations and Difficulties

References

Chapter 15: Obesity and Metabolic Syndrome

15.1 Introduction

15.2 Why Metabolic Syndrome?

15.3 Classical Animal Models of Obesity and Metabolic Syndrome

15.4 Human Experimental Models

15.5 Translation to Clinics: Difficulties and Limitations

References

Chapter 16: Cognitive Disorders: Impairment, Aging, and Dementia

16.1 Introduction

16.2 Pharmacological Models

16.3 Aging and Transgenic Models

16.4 Translation to Clinics: Limitations and Difficulties

References

Chapter 17: Stroke and Traumatic Brain Injury

17.1 Introduction

17.2 Stroke Models

17.3 Traumatic Brain Injury Models

17.4 Outcome Assessment

17.5 Translation to Clinics: Limitations and Difficulties

References

Chapter 18: Movement Disorders: Parkinson's Disease

18.1 Introduction

18.2 Drug- and Toxin-Based Models of PD

18.3 Genetic and Functional Models of PD

18.4 Translation to Clinics: Limitations and Difficulties

References

Chapter 19: Epilepsy: Animal Models to Reproduce Human Etiopathology

19.1 Introduction

19.2 What Animal Species to Use to Model Epilepsy?

19.3 Which Type of Models Provide the Most Reliable Information on the Pathophysiology of Epilepsies?

19.4 Modeling Four Prototypic Forms of Epilepsy

19.5 Translation to Clinics: Limitations and Difficulties

References

Chapter 20: Lung Diseases

20.1 Introduction

20.2 Animal Models of Lung Emphysema or Chronic Obstructive Pulmonary Disease

20.3 Animal Models of Pulmonary Hypertension

20.4 Animal Models of Fibrotic Lung Diseases

20.5 Animal Models of Acute Respiratory Distress Syndrome

20.6 Translation to Clinics: Limitations and Difficulties

References

Chapter 21: Heart Failure

21.1 Introduction

21.2 Hypertension-Related Heart Failure

21.3 Pressure and Volume Overload-Induced Heart Failure

21.4 Toxic Molecule-Induced Heart Failure

21.5 Heart Failure Models Related to Myocardial Ischemia and/or Myocardial Infarction

21.6 Pacing-Induced Heart Failure

21.7 Gene Mutation-Induced Cardiomyopathies

21.8 Translation to Clinics: Limitations and Difficulties

References

Chapter 22: Endocrine Disorders

22.1 Introduction

22.2 Animal Models in Autoimmune Endocrine Diseases

22.3 Animal Models in Endocrine Tumors

22.4 Animal Models in Endocrine Physiology: Organogenesis, Reproduction, and Metabolism

22.5 Translation to Clinics: Limitations and Difficulties

References

Chapter 23: Gastrointestinal Disorders: A Patho-biotechnology Approach to Probiotic Therapy

23.1 Introduction

23.2 Delivery: Improving Probiotic Resistance to Process-Induced Stresses and Storage Conditions

23.3 Survival: Improving Probiotic–Host Colonization

23.4 Efficacy: “Designer Probiotics”

23.5 Translation to Clinics: Limitations and Difficulties

References

Chapter 24: Renal Disorders

24.1 Introduction

24.2 Animal Models

24.3 Translation to Clinics: Limitations and Difficulties

References

Chapter 25: Genitourinary Disorders: Lower Urinary Tract and Sexual Functions

25.1 Introduction

25.2 Lower Urinary Tract Function

25.3 Sexual Functions

25.4 Translation to Clinics: Difficulties and Limitations

References

Index

End User License Agreement

List of Tables

Table 2.1

Table 2.2

Table 2.3

Table 2.4

Table 2.5

Table 2.6

Table 3.1

Table 3.2

Table 5.1

Table 5.2

Table 5.3

Table 5.4

Table 6.1

Table 6.2

Table 7.1

Table 9.1

Table 11.1

Table 11.2

Table 12.1

Table 13.1

Table 13.2

Table 13.3

Table 14.1

Table 15.1

Table 15.2

Table 15.3

Table 16.1

Table 16.2

Table 16.3

Table 17.1

Table 18.1

Table 20.1

Table 22.1

Table 22.2

Table 22.3

Table 22.4

Table 22.5

Table 24.1

Table 24.2

List of Illustrations

Figure 1.1

Figure 2.1

Figure 2.2

Figure 7.1

Figure 7.2

Figure 8.1

Figure 8.2

Figure 8.3

Figure 8.4

Figure 9.1

Figure 9.2

Figure 9.3

Figure 11.1

Figure 11.2

Figure 11.3

Figure 14.1

Figure 14.2

Figure 17.1

Figure 20.1

Figure 20.2

Figure 20.3

Figure 21.1

Figure 21.2

Figure 22.1

Figure 22.2

Figure 22.3

Figure 23.1

Figure 23.2

Figure 25.1

Figure 25.2

Figure 25.3

Figure 25.4

Figure 25.5

Figure 25.6

Figure 25.7

Guide

Cover

Table of Contents

Preface

Part 1

Chapter 1

Pages

ii

iii

iv

xix

xx

xxi

xxii

xxiii

xxiv

xxv

xxvi

xxvii

xxix

xxx

xxxi

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

22

23

24

25

26

27

28

29

30

31

32

33

34

35

36

37

38

39

40

41

42

43

44

45

46

47

48

49

50

51

52

53

54

55

56

57

58

59

60

61

62

63

64

65

66

67

68

69

70

71

72

73

74

75

76

77

78

79

80

81

82

83

84

85

86

87

88

89

90

91

92

93

94

95

96

97

98

99

100

101

102

103

104

105

106

107

108

109

110

111

112

113

114

115

116

117

118

119

120

121

122

123

124

125

126

127

128

129

130

131

132

133

134

135

136

137

138

139

140

141

142

143

144

145

146

147

148

149

150

151

152

153

154

155

156

157

158

159

160

161

162

163

164

165

166

167

168

169

170

171

172

173

174

175

176

177

178

179

180

181

182

183

184

185

186

187

188

189

190

191

192

193

194

195

196

197

198

199

200

201

202

203

204

205

206

207

208

209

210

211

212

213

214

215

216

217

218

219

220

221

222

223

224

225

226

227

228

229

230

231

232

233

234

235

236

237

238

239

240

241

242

243

244

245

246

247

248

249

250

251

252

253

254

255

256

257

258

259

260

261

262

263

264

265

266

267

268

269

270

271

272

273

274

275

276

277

278

279

280

281

282

283

284

285

286

287

288

289

290

291

292

293

294

295

296

297

298

299

300

301

302

303

304

305

306

307

308

309

310

311

312

313

314

315

316

317

318

319

320

321

322

323

324

325

326

327

328

329

330

331

332

333

334

335

336

337

338

339

340

341

342

343

344

345

346

347

348

349

350

351

352

353

354

355

356

357

358

359

360

361

362

363

364

365

366

367

368

369

370

371

372

373

374

375

376

377

378

379

380

381

382

383

384

385

386

387

388

389

390

391

392

393

394

395

396

397

398

399

400

401

402

403

404

405

406

407

408

409

410

411

412

413

414

415

416

417

418

419

420

421

422

423

424

425

426

427

428

429

430

431

432

433

434

435

436

437

438

439

440

441

442

443

444

445

446

447

448

449

450

451

452

453

454

455

456

457

458

459

460

461

462

463

464

465

466

467

468

469

470

471

472

473

474

475

476

477

478

479

480

481

482

483

484

485

486

487

488

489

490

491

492

493

494

495

496

497

498

499

500

501

502

503

504

505

506

507

508

509

510

511

512

513

514

515

516

517

518

519

520

521

522

523

524

525

526

527

528

529

530

531

532

533

534

535

536

537

538

539

540

541

542

543

544

545

546

547

548

549

550

551

552

553

554

555

556

557

558

559

560

561

562

Methods and Principles in Medicinal Chemistry

Edited by R. Mannhold, H. Kubinyi, G. Folkers

Editorial Board

H. Buschmann, H. Timmerman, H. van de Waterbeemd, T. Wieland

Previous Volumes of this Series:

Liras, Spiros / Bell, Andrew S. (Eds.)

Phosphodiesterases and Their Inhibitors

2014

ISBN: 978-3-527-33219-9

Vol. 61

Hanessian, Stephen (Ed.)

Natural Products in Medicinal Chemistry

2014

ISBN: 978-3-527-33218-2

Vol. 60

Lackey, Karen / Roth, Bruce (Eds.)

Medicinal Chemistry Approaches to Personalized Medicine

2013

ISBN: 978-3-527-33394-3

Vol. 59

Brown, Nathan (Ed.)

Scaffold Hopping in Medicinal Chemistry

2013

ISBN: 978-3-527-33364-6

Vol. 58

Hoffmann, Rémy / Gohier, Arnaud / Pospisil, Pavel (Eds.)

Data Mining in Drug Discovery

2013

ISBN: 978-3-527-32984-7

Vol. 57

Dömling, Alexander (Ed.)

Protein-Protein Interactions in Drug Discovery

2013

ISBN: 978-3-527-33107-9

Vol. 56

Kalgutkar, Amit S. / Dalvie, Deepak / Obach, R. Scott / Smith, Dennis A.

Reactive Drug Metabolites

2012

ISBN: 978-3-527-33085-0

Vol. 55

Brown, Nathan (Ed.)

Bioisosteres in Medicinal Chemistry

2012

ISBN: 978-3-527-33015-7

Vol. 54

Gohlke, Holger (Ed.)

Protein-Ligand Interactions

2012

ISBN: 978-3-527-32966-3

Vol. 53

Kappe, C. Oliver / Stadler, Alexander / Dallinger, Doris

Microwaves in Organic and Medicinal Chemistry

Second, Completely Revised and Enlarged Edition

2012

ISBN: 978-3-527-33185-7Vol. 52

In Vivo Models for Drug Discovery

Edited by José M. Vela

Rafael Maldonado

Michel Hamon

All books published by Wiley-VCH are carefully produced. Nevertheless, authors, editors, and publisher do not warrant the information contained in these books, including this book, to be free of errors. Readers are advised to keep in mind that statements, data, illustrations, procedural details or other items may inadvertently be inaccurate.

Library of Congress Card No.: applied for

British Library Cataloguing-in-Publication Data

A catalogue record for this book is available from the British Library.

Bibliographic information published by the Deutsche Nationalbibliothek

The Deutsche Nationalbibliothek lists this publication in the Deutsche Nationalbibliografie; detailed bibliographic data are available on the Internet at <http://dnb.d-nb.de>.

©2014 Wiley-VCH Verlag GmbH & Co. KGaA, Boschstr. 12, 69469 Weinheim, Germany

All rights reserved (including those of translation into other languages). No part of this book may be reproduced in any form – by photoprinting, microfilm, or any other means – nor transmitted or translated into a machine language without written permission from the publishers. Registered names, trademarks, etc. used in this book, even when not specifically marked as such, are not to be considered unprotected by law.

Print ISBN:978-3-527-33328-8

ePDF ISBN:978-3-527-67937-9

ePub ISBN:978-3-527-67936-2

mobi ISBN:978-3-527-67935-5

oBook ISBN:978-3-527-67934-8

List of Contributors

Serge Adnot

Université Paris-Est Créteil (UPEC)

Faculté de Médecine

Hôpital Henri Mondor

51 Avenue du Maréchal de Lattre de Tassigny

94010 Créteil Cedex

France

Denis Ardid

Clermont Université (Université d'Auvergne)

NEURO-DOL

Faculté de médecine

Place Henri Dunant

63000 Clermont-Ferrand

France

and

INSERM U1107

63001 Clermont-Ferrand

Faculté de médecine

Place Henri Dunant

France

David Balayssac

Clermont Université (Université d'Auvergne)

NEURO-DOL

63000 Clermont-Ferrand

France

and

INSERM U1107

63001 Clermont-Ferrand

Faculté de médecine

Place Henri Dunant

France

and

CHU Clermont-Ferrand

Toxicoloy department

63003 Clermont-Ferrand

France

Anne Barlier

AP-HM, Conception

Laboratory of Molecular Biology

147 Bd Baille

13855 Marseille Cedex

France

and

Aix-Marseille University

Faculté de Médecine Nord

Laboratoire CRN2M, UMR 7286 CNRS

51 Bd Pierre Dramard

13344 Marseille Cedex 15

France

Sandra Beeské

Sanofi

Exploratory Unit

1 avenue Pierre Brossolette

91385 Chilly-Mazarin

France

Delphine Behr-Roussel

Pelvipharm Laboratories

2, avenue de la source de la Biévre

78390 Montigny le Bretonneux

France

and

University of Versailles-St Quentin en Yvelines

School of Health Sciences

SIRIUS/EA4501

2, avenue de la source de la Biévre

78390 Montigny le Bretonneux

France

Alain Berdeaux

Université Paris-Est Créteil (UPEC)

Faculté de Médecine

Laboratoire de Pharmacologie

INSERM U955 (équipe 3 IMRB)

Rue du Général Sarrail, 8

94010 Créteil Cedex

France

Valérie C. Besson

Université Paris Descartes

Faculté de Pharmacie

Laboratoire de Pharmacologie

EA 4475 “Pharmacologie de la Circulation Cérébrale”

4, avenue de l'Observatoire

75006 Paris Cedex 06

France

Maharshi Bhaswant

Victoria University

College of Health & Biomedicine

St Albans, Melbourne 3021

Australia

Jorge Boczkowski

Université Paris-Est Créteil (UPEC)

Faculté de Médecine

Hôpital Henri Mondor

51 Avenue du Maréchal de Lattre de Tassigny

94010 Créteil Cedex

France

Sylvie Bourgoin

Université Pierre et Marie Curie

Faculty of Medicine

Neuropsychopharmacology Unit

INSERM U894 – CPN

site Pitié-Salpêtrière

91, boulevard de l'Hôpital

75634 Paris Cedex 13

France

Laurent Boyer

Université Paris-Est Créteil (UPEC)

Faculté de Médecine

Hôpital Henri Mondor

51 Avenue du Maréchal de Lattre de Tassigny

94010 Créteil Cedex

France

Véronique Brault

Université de Strasbourg

Institut Clinique de la Souris

ICS-MCI, PHENOMIN, GIE CERBM

CNRS, INSERM

1 rue Laurent Fries

67404 Illkirch

France

and

Université de Strasbourg

Institut de Génétique Biologie Moléculaire et Cellulaire

IGBMC, GIE CERBM

CNRS, INSERM

UMR7104, UMR964

1 rue Laurent Fries

67404 Illkirch

France

Lindsay Brown

University of Southern Queensland

School of Health Nursing and Midwifery Toowoomba, Queensland 4350

Australia

Christos Chatziantoniou

Inserm UMR S 1155 Sorbonne Université UPMC Univ Paris 06 4 rue de la Chine 75020 Paris

France

and

Université Pierre et Marie Curie

Paris

France

Fabien Chauveau

Université Lyon 1

Lyon Neuroscience Research Center

CNRS, INSERM

59 Bd Pinel

69003 Lyon

France

and

CERMEP-Imagerie du Vivant

Lyon

France

Sarah Louise T. Christensen

University of Copenhagen

Faculty of Health Sciences

Glostrup Hospital

Department of Neurology and Glostrup Research Institute

Danish Headache Center

Nordre Ringvej 57

2600 Glostrup

Denmark

Pierre Clément

Pelvipharm Laboratories

2, avenue de la source de la Biévre

78390 Montigny le Bretonneux

France

and

University of Versailles-St Quentin en Yvelines

School of Health Sciences

SIRIUS/EA4501

2, avenue de la source de la Biévre

78390 Montigny le Bretonneux

France

Thomas Cuny

University Hospital of Nancy-Brabois

Department of Endocrinology and Medical Gynaecology

Rue du Morvan 54511 Vandoeuvre-Les-Nancy Cedex

France

and

Aix-Marseille University

Faculté de Médecine Nord

Laboratoire CRN2M, UMR 7286 CNRS

51 Bd Pierre Dramard

13344 Marseille Cedex 15

France

Yassine Darbaky

ANS Biotech

Faculté de Médecine et de

Pharmacologie

28, place Henri Dunant

63000 Clermont-Ferrand

France

Antoine Depaulis

INSERM U836

Dynamics of Epileptic Synchronous

Networks

38042 Grenoble Cedex 9

France

and

Université Joseph Fourier

Grenoble Institut des Neurosciences

38042 Grenoble Cedex 9

France

Ronan Depoortère

Centre de Recherche Pierre-Fabre

Neuropsychopharmacology Unit

17 avenue Jean Moulin

81106 Castres

France

Laurent Diop

ANS Biotech

Faculté de Médecine et de Pharmacologie

28, place Henri Dunant

63000 Clermont-Ferrand

France

Jean-Claude Dussaule

Inserm UMR S 1155 Sorbonne Universités UPMC Univ Paris 06 4 rue de la Chine 75020 Paris

France

and

Saint-Antoine Hospital

HUEP, AP-HP Department of Physiology

184 rue du faubourg Saint-Antoine, 75012 Paris

France

Alain Enjalbert

AP-HM, Conception

Laboratory of Molecular Biology

147 Bd Baille 13855 Marseille Cedex

France

and

Aix-Marseille University

Faculté de Médecine Nord

Laboratoire CRN2M, UMR 7286 CNRS

51 Bd Pierre Dramard

13344 Marseille Cedex 15

France

François Giuliano

Pelvipharm Laboratories

2, avenue de la source de la Biévre

78390 Montigny le Bretonneux

France

and

University of Versailles-St Quentin en Yvelines

School of Health Sciences

SIRIUS/EA4501

2, avenue de la source de la Biévre

78390 Montigny le Bretonneux

France

and

Raymond Poincaré Hospital

Department of Physical Medicine and Rehabilitation

Neuro-Uro-Andrology

AP-HP

104, boulevard Raymond Poincaré

92380 Garches

France

Christopher G. Goetz

Rush University Medical Center

Department of Neurology

1725 West Harrison Street

Chicago, IL 60612

USA

Guy Griebel

Sanofi

Exploratory Unit

1 avenue Pierre Brossolette

91385 Chilly-Mazarin

France

Dominique Guerrot

INSERM Unit 1096 Rouen University Medical School 22 Boulevard Gambetta 76183 Rouen France

and

Rouen University Hospital Department of Nephrology 1 rue de Germont 76031 Rouen France

Isabelle Guillemain

INSERM U836

Dynamics of Epileptic Synchronous Networks

38042 Grenoble Cedex 9

France

and

Université Joseph Fourier

Grenoble Institut des Neurosciences

38042 Grenoble Cedex 9

France

Javier Gutiérrez-Cuesta

Universitat Pompeu Fabra

Laboratori de Neurofarmacologia

Parc de Recerca Biomedica de Barcelona (PRBB)

Dr. Aiguader 88

08003 Barcelona

Spain

Antonio Guzmán

Esteve

Department of Toxicology

Drug Discovery & Preclinical Development

Parc Cientific Barcelona

Baldiri Reixac 4–8

08028 Barcelona

Spain

Michel Hamon

Université Pierre et Marie Curie

Faculty of Medicine

Neuropsychopharmacology Unit

INSERM U894 – CPN

site Pitié-Salpêtrière

91, boulevard de l'Hôpital

75634 Paris Cedex 13

France

Christophe Heinrich

INSERM U836

Dynamics of Epileptic Synchronous Networks

38042 Grenoble Cedex 9

France

and

Université Joseph Fourier

Grenoble Institut des Neurosciences

38042 Grenoble Cedex 9

France

Yann Hérault

Université de Strasbourg

Institut Clinique de la Souris

ICS-MCI, PHENOMIN, GIE CERBM

CNRS, INSERM

1 rue Laurent Fries

67404 Illkirch

France

and

Université de Strasbourg

Institut de Génétique Biologie Moléculaire et Cellulaire

IGBMC, GIE CERBM

CNRS, INSERM

UMR7104, UMR964

1 rue Laurent Fries

67404 Illkirch

France

and

Transgenèse et Archivage d'Animaux Modèles

TAAM UPS44, CNRS, PHENOMIN

3B rue de la Férollerie

45071 Orléans Cedex 2

France

Houman Homayoun

University of Pittsburgh Medical Center

Department of Neurology

3471 Fifth Ave, suite 810

Pittsburgh, PA 15213

USA

Inger Jansen-Olesen

University of Copenhagen

Faculty of Health Sciences

Glostrup Hospital

Department of Neurology and Glostrup Research Institute

Danish Headache Center

Nordre Ringvej 57

2600 Glostrup

Denmark

Konstantinos Kompotis

Maastricht University

School for Mental Health and Neuroscience

Department of Neuroscience

Universiteitssingel 50

6229 ER Maastricht

The Netherlands

Roy Lardenoije

Maastricht University

School for Mental Health and Neuroscience

Department of Neuroscience

Universiteitssingel 50

6229 ER Maastricht

The Netherlands

Dominique Lerouet

Université Paris Descartes

Faculté de Pharmacie

Laboratoire de Pharmacologie

EA 4475 “Pharmacologie de la Circulation Cérébrale”

4, avenue de l'Observatoire

75006 Paris Cedex 06

France

Rafael Maldonado

Universitat Pompeu Fabra

Department of Experimental & Health Sciences

Laboratory of Neuropharmacology (NeuroPhar)

Barcelona Biomedical Research Park (PRBB)

Dr. Aiguader 88

08003 Barcelona

Spain

Christophe Mallet

Clermont Université (Université d'Auvergne)

NEURO-DOL

Faculté de médecine Place Henri Dunant

63000 Clermont-Ferrand

France

and

INSERM U1107

Faculté de médecine Place Henri Dunant

63001 Clermont-Ferrand

France

Elena Martín-García

Universitat Pompeu Fabra

Laboratori de Neurofarmacologia

Parc de Recerca Biomedica de Barcelona (PRBB)

Dr. Aiguader 88

08003 Barcelona

Spain

Said M'Dahoma

Université Pierre et Marie Curie

Faculty of Medicine

Neuropsychopharmacology Unit

INSERM U894 – CPN

site Pitié-Salpêtrière

91, boulevard de l'Hôpital

75634 Paris Cedex 13

France

Armand Mekontso-Dessap

Université Paris-Est Créteil (UPEC)

Hôpital Henri Mondor

Service de Réanimation Médicale

AP-HP

94010 Créteil Cedex

France

Paul Moser

Centre de Recherche Pierre-Fabre

Neuropsychopharmacology Unit

17 avenue Jean Moulin

81106 Castres

France

Jes Olesen

University of Copenhagen

Faculty of Health Sciences

Glostrup Hospital

Department of Neurology and Glostrup Research Institute

Danish Headache Center

Nordre Ringvej 57

2600 Glostrup

Denmark

Sunil K. Panchal

University of Southern Queensland Centre for Systems Biology

Toowoomba, Queensland 4350

Australia

Guillaume Pavlovic

Université de Strasbourg

Institut Clinique de la Souris

ICS-MCI, PHENOMIN, GIE CERBM

CNRS, INSERM

1 rue Laurent Fries

67404 Illkirch

France

Michel Plotkine

Université Paris Descartes

Faculté de Pharmacie

Laboratoire de Pharmacologie

EA 4475 “Pharmacologie de la Circulation Cérébrale”

4, avenue de l'Observatoire

75006 Paris Cedex 06

France

Jos Prickaerts

Maastricht University

School for Mental Health and Neuroscience

Department of Neuroscience

Universiteitssingel 50

6229 ER Maastricht

The Netherlands

Patricia Robledo

Universitat Pompeu Fabra

Laboratori de Neurofarmacologia

Parc de Recerca Biomedica de Barcelona (PRBB)

Dr. Aiguader 88

08003 Barcelona

Spain

and

IMIM-Hospital del Mar Research Institute

Human Pharmacology and Clinical Neurosciences Research Group

Neurosciences Research Programme

PRBB

Calle Dr. Aiguader 88

08003 Barcelona

Spain

Luz Romero

Esteve

Drug Discovery & Preclinical Development

Parc Cientific Barcelona

Baldiri Reixac 4–8

08028 Barcelona

Spain

Bart P.F. Rutten

Maastricht University

School for Mental Health and Neuroscience

Department of Neuroscience

Universiteitssingel 50

6229 ER Maastricht

The Netherlands

David Sabaté

Esteve

R&D Department Animal Health Division

Animal Ethics Committee

Avinguda Mare de Déu de Montserrat, 221

08041 Barcelona

Spain

Roy D. Sleator

Cork Institute of Technology

Department of Biological Sciences

Rossa Avenue

Bishopstown, Cork

Ireland

Tania Sorg

Université de Strasbourg

Institut Clinique de la Souris

ICS-MCI, PHENOMIN, GIE CERBM

CNRS, INSERM

1 rue Laurent Fries

67404 Illkirch

France

Harry W.M. Steinbusch

Maastricht University

School for Mental Health and Neuroscience

Department of Neuroscience

Universiteitssingel 50

6229 ER Maastricht

The Netherlands

and

Maastricht University School for Mental Health and Neuroscience

Department of Neuroscience Universiteitssingel 506229 ER Maastricht The Netherlands

Jin Bo Su

Université Paris-Est Créteil (UPEC)

Faculté de Médecine

Laboratoire de Pharmacologie

INSERM U955 (équipe 3 IMRB)

Rue du Général Sarrail, 8

94010 Créteil Cedex

France

Nick P. van Goethem

Maastricht University

School for Mental Health and Neuroscience

Department of Neuroscience

Universiteitssingel 50

6229 ER Maastricht

The Netherlands

José Miguel Vela

Esteve

Drug Discovery & Preclinical Development

Parc Cientific Barcelona

Baldiri Reixac 4–8

08028 Barcelona

Spain

Mathieu Verdurand

Université Lyon 1

Lyon Neuroscience Research Center

CNRS, INSERM

59 Bd Pinel, 69003 Lyon

France

and

CERMEP-Imagerie du Vivant

Lyon

France

Luc Zimmer

Université Lyon 1

Lyon Neuroscience Research Center

CNRS, INSERM

59 Bd Pinel, 69003 Lyon

France

and

CERMEP-Imagerie du Vivant

59 Bd Pinel, 69003 Lyon

France

and

Hospices Civils de Lyon

Groupement Hospitalier Est

59 Bd Pinel, 69003 Lyon

France

Preface

Once, in a zoo, the chief of a gorilla group had to visit a dentist. He was not easily persuaded and finally, someone advised to mix a “sleeping pill” in his food. This suggestion was fiercely refused by the veterinarians, because they did not want to expose a precarious zoo animal to therapeutics that had been developed for humans.

The anecdote nicely depicts the experts' subliminal discomfort about the comparability of drug action in “humans and mice,” which is an ongoing and often an ideological debate in drug development. Many of the arguments in the debate touch fundamental questions as the position of man within the realm of evolution theory [1], or request the full abandonment of any animal test in drug development, since animals that “lead biographical lives” are not different with respect to man's position in evolution [2]. The underlying uncertainty among scientists is raised by the question whether and how animals emotionally judge and reflect on the environments and if so, in which way this activity influences their physiology. Modern brain research has opened Pandora's box by exposing rodents to enriched environment and demonstrating phenotype plasticity [3]. What is then the validity of current animal models of mental disorders?