Animal Models of Cognitive Impairment

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ISBN: 9780849328343 | 0849328349
Cover: Hardcover
Copyright: 6/22/2006

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The costs associated with a drug's clinical trials are so significant that it has become necessary to validate both its safety and efficacy in animal models prior to the continued study of the drug in humans.Featuring contributions from distinguished researchers in the field of cognitive therapy research, Animal Models of Cognitive Impairment examines some of the most popular and successful animal archetypes used in the context of drug discovery. It provides integrated coverage of the latest research concerning neuronal systems relevant to cognitive function and dysfunction, assimilating reviews of this research within the context of each chapter. This approach is unique in that it brings together molecular and neurochemical methodologies, behavioral applications in translational models, and clinical applications.The book comprehensively discusses a wide variety of animal models of cognitive impairment, including genetic, lesion, pharmacological, and aging related impairments. It also explores the significance of this research in regards to the treatment of various addictions and disorders such as stroke, autism, Alzheimer's, schizophrenia, and ADHD.Edited by two renowned authorities in the field, Animal Models of Cognitive Impairment is a timely book that provides integrated coverage of cutting-edge research that concerns neuronal systems relevant to cognitive function and dysfunction.

Chapter 1 Introduction

(4)

Edward D. Levin and Jerry J. Buccafusco

SECTION I Pharmacologic Models

Chapter 2 Muscarinic Receptor Antagonists in Rats

(16)

Alvin V. Terry, Jr.

Introduction

(1)

Memory-Related Task Impairment in Rats by Scopolamine and Other Antimuscarinic Agents

(2)

The Nature of the Effects of Antimuscarinics on Memory Performance (Potential Limitations)

(1)

Other Limitations and Criticisms of the Use of Antimuscarinics as Amnestic Agents

(3)

Scopolamine-Reversal Studies and Drug Discovery

(2)

Conclusions

(1)

References

(7)

Chapter 3 Nicotinic Receptor Antagonists in Rats

(16)

Cindy S. Roegge and Edward D. Levin

Introduction

(1)

Radial Arm Maze (RAM)

(2)

Three-Panel Runway Task

(1)

T-Maze Alternation

(1)

T-Maze Discrimination

(1)

Delayed (Non)Matching to Sample

(3)

Tests of Sustained Attention

(1)

Tests of Response Inhibition

(1)

Water Maze

(1)

Avoidance Learning

(2)

Conclusions

(1)

References

(5)

Chapter 4 Involvement of the NMDA System in Learning and Memory

(12)

Amir H. Rezvani

Introduction

(1)

Animal Studies

(5)

NMDA

(1)

Transgenic and Mutant Mice

(1)

NMDA Antagonists

(3)

NMDA Transporter Inhibitors

(1)

Human Studies

(2)

Conclusions

(1)

References

(5)

Chapter 5 Animal Models and the Cognitive Effects of Ethanol

(24)

Merle G. Paule

Background

(2)

Behavioral Effects in Animal Models

(13)

Relevance

(1)

Mechanism(s) of Action of Ethanol

(1)

Subjective Effects: Drug Discrimination Studies

(6)

Effects of Ethanol on Other Aspects of Cognition: Attention, Learning, and Memory

(1)

Attention/Impulsivity

(1)

Conditioning

(1)

Learning and Memory

(1)

Working/Short-Term Memory

(3)

Comparative Sensitivities of Different Cognitive Functions to the Effects of Ethanol

(1)

Age-Related Differences in Sensitivity to Ethanol

(1)

Environmental and Other Influences on the Effects of Ethanol

(1)

Overview

(1)

References

(9)

SECTION II Toxicologic Models

Chapter 6 Animal Models of Cognitive Impairment Produced by Developmental Lead Exposure

(28)

Deborah C. Rice

Intermittent Schedules of Reinforcement

(3)

Learning

(6)

Memory

(6)

Attention

(3)

Sensory Dysfunction: Possible Contribution to "Cognitive" Effects

(2)

Conclusions

(1)

References

(6)

Chapter 7 Developmental Behavioral Toxicity of Methylmercury: Consequences, Conditioning, and Cortex

101

(46)

M. Christopher Newland, Wendy D. Donlin, Elliott M. Paletz, and Kelly M. Banna

Mercury Forms and Sources

102

(2)

Human Exposures

104

(1)

Developmental Exposure

104

(1)

Adult-Onset Exposure

104

(1)

Nutrition

105

(1)

Selenium

105

(1)

Docosahexaenoic Acid (DHA)

105

(1)

Neurotoxicants and Behavioral Plasticity

106

(2)

Identifying Effects of MeHg Exposure on Learning

108

(1)

Choice

108

(10)

Choice in Steady-State Conditions

110

(2)

Neurotoxicant Exposure and Choice

112

(1)

Choice in Transition

112

(6)

Acquisition of Fixed-Ratio (FR) Responding

118

(3)

Differential Reinforcement of High-Rate Behavior

121

(4)

Motor Function

125

(1)

Sensory Deficits

126

(1)

Discrimination and Memory Processes

126

(2)

Drug Challenges

128

(1)

Neural and Behavioral Mechanisms

128

(6)

MeHg and the Response-Reinforcer Relationship

129

(2)

Dopamine, the Cortex, and Response-Reinforcer Relationships

131

(2)

Neural Effects of MeHg Exposure

133

(1)

Conclusion

134

(1)

References

135

(12)

Chapter 8 Executive Function following Developmental Exposure to Polychlorinated Biphenyls (PCBs): What Animal Models Have Told Us

147

(22)

Helen J.K. Sable and Susan L. Schantz

Introduction

147

(1)

Classes of PCB Congeners

148

(1)

Ortho-Substituted PCB Congeners

149

(15)

Cognitive Flexibility

149

(4)

Working Memory

153

(7)

Inhibitory Control

160

(4)

Conclusions

164

(1)

Acknowledgments

164

(1)

References

164

(5)

Chapter 9 Modeling Cognitive Deficits Associated with Parkinsonism i the Chronic-Low-Dose MPTP-Treated Monkey

169

(14)

J.S. Schneider

Cognitive Deficits Associated with Parkinson's Disease

169

(1)

Modeling Cognitive Deficits of Parkinsonism with Chronic Administration of MPTP

170

(1)

Attentional and Executive Function Deficits Characterize "Early" Parkinsonian MPTP-Treated Monkeys

171

(5)

Attentional/Executive Tasks

172

(1)

Effects of Chronic Low Dose MPTP Exposure

173

(3)

Relevance of the Chronic-Low-Dose MPTP Monkey Model to Other Disorders

176

(1)

Conclusions

177

(1)

Acknowledgments

177

(1)

References

177

(6)

SECTION III Mouse Genetic Models

Chapter 10 Cognitive Impairment in Transgenic Mouse Models of Amyloid Deposition

183

(16)

Dave Morgan

Introduction

183

(1)

Memory Deficits Correlate with Aβ Load

184

(2)

Interventions Improving Memory in APP Transgenic Mice

186

(3)

Mechanisms of Aβ-Associated Memory Impairment in Transgenic Mice

189

(2)

Conclusions

191

(1)

Acknowledgments

192

(1)

References

192

(7)

Chapter 11 Cholinergic Receptor Knockout Mice

199

(24)

Lu Zhang

Muscarinic Acetylcholine Receptors (mAChRs)

201

(16)

Generation of mAChR KO Mice

201

(1)

General Observations in mAChR KO Mice

202

(1)

Cognitional Data with mAChR KO Mice

203

(1)

M1 mAChR KO Mice (M1 Receptor-Deficient Mice)

203

(1)

M2 mAChR KO Mice (M2 Receptor-Deficient Mice)

206

(1)

M3 mAChR KO Mice

207

(1)

M4 mAChR KO Mice

207

(1)

M5 mAChR KO Mice

207

(1)

Double M1 and M3 mAChR KO Mice

208

(1)

Double M2 and M4 mAChR KO Mice

208

(1)

Nicotinic Acetylcholine Receptors (nAChRs)

208

(1)

Generation of nAChR KO Mice

208

(1)

General Observations in nAChR KO Mice

209

(1)

Cognitional Data with nAChR KO Mice

209

(1)

β2 nAChR KO Mice

210

(1)

α4 nAChR KO Mice

211

(1)

α7 nAChR KO Mice

211

(1)

Cholinesterases

211

(1)

Generation of AChE KO Mice (Acetylcholinesterase -/- Mice or Nullizygous)

211

(1)

General Observations in AChE KO Mice

211

(1)

Cognitional Data with AChE KO Mice

212

(1)

Limitations with Gene-Targeting (Knockout) Approach and Future Directions

212

(1)

Genetic Background

213

(1)

Developmental and Functional Compensation

214

(1)

Redundant Mechanism

215

(1)

Refined Gene-Targeting Technology

215

(1)

Classical Pharmacological Approaches

216

(1)

References

217

(6)

Chapter 12 Assessments of Cognitive Deficits in Mutant Mice

223

(62)

Ramona Marie Rodriguiz and William C. Wetsel

Preliminary Phenotypic Screening

225

(5)

Anxiety

226

(1)

Open Field

227

(1)

Neurophysiological Screen

227

(3)

Cognitive Testing

230

(11)

Preattentive Processes

230

(3)

Attention

233

(1)

Orienting Responses

233

(1)

Multiple-Choice Serial-Reaction Test

235

(1)

Go/No-Go (GNG) Testing

238

(1)

Latent Inhibition (LI)

240

(1)

Learning and Memory

241

(27)

Associative Learning

241

(2)

Avoidance Tests

243

(1)

Passive Avoidance

244

(1)

One-Way Active Avoidance

245

(1)

Two-Way Active (Shuttle) Avoidance

246

(1)

Nonspatial Learning

247

(1)

Object-Discrimination Test

247

(1)

Social Transmission of Food Preference

248

(1)

Nonspatial Transverse-Pattern Test

250

(2)

Spatial and Contextual Learning

252

(1)

Radial Arm Maze

253

(1)

Morris Water Maze

254

(3)

Neurological Mechanisms Underlying Learning and Memory

257

(3)

Conditioned Emotional Responses

260

(1)

Conditioned Taste Aversion (CTA)

260

(1)

Fear-Potentiated Startle (FPS)

262

(1)

Fear Conditioning

264

(4)

Summary and Comments

268

(1)

Appendix: Shock-Threshold Testing

268

(1)

References

269

(16)

SECTION IV Model Applications and Future Developments

Chapter 13 Cognitive Pharmacology in Aging Macaques

285

(16)

Jerry J. Buccafusco

Cognitive Changes with Age in Macaques

285

(2)

Do Old Monkeys Get Alzheimer's(-like) Disease?

286

(1)

Delayed Matching-to-Sample as a Paradigm for Assessing Cognition

287

(4)

A Computer-Automated Procedure

287

(1)

Seventeen Years of Testing Cognition-Enhancing Drugs

288

(1)

Age-Related Differences in the Actions of Cognition-Enhancing Drugs

289

(2)

Cognitive Changes with Age in Macaques and Man

291

(6)

Macaque Data

291

(4)

Human Data

295

(2)

Future Directions

297

(1)

Acknowledgments

298

(1)

References

298

(3)

Chapter 14 Cognitive Impairment following Traumatic Brain Injury

301

(14)

Mark D. Whiting, Anna I. Baranova, and Robert J. Hamm

Introduction

301

(2)

Animal Models of Traumatic Brain Injury

302

(1)

Fluid Percussion

302

(1)

Weight Drop/Impact Acceleration

302

(1)

Closed Cortical Impact

303

(1)

Information Processing: A Brief Overview

303

(1)

Memory Impairment after TBI

303

(8)

Retrograde Amnesia

303

(3)

Working Memory

306

(1)

Anterograde Amnesia

307

(2)

Age Effects on Memory Impairment after TBI

309

(1)

Comparing Experimental Models

310

(1)

Conclusion

311

(1)

References

312

(3)

Chapter 15 Cognitive Impairment Models Using Complementary Species

315

(28)

Daniel T. Cerutti and Edward D. Levin

Fish Models

315

(15)

Goldfish (Carassius auratus)

317

(1)

Reflexes and Habituation

318

(1)

Pavlovian Conditioning

318

(1)

Operant Conditioning

319

(1)

Maze Learning

321

(1)

Summary

322

(1)

Zebrafish (Danio rerio)

322

(1)

Reflexes and Habituation

322

(1)

Pavlovian Conditioning

324

(1)

Operant Conditioning

324

(1)

Mazes

325

(1)

Summary

326

(1)

Invertebrate Models

327

(1)

C. Elegans

328

(1)

Drosophila

329

(1)

Conclusions

330

(1)

Acknowledgments

330

(1)

References

330

(13)

Chapter 16 Cognition Models and Drug Discovery

343

(12)

Michael W. Decker

Introduction

343

(1)

Considerations in the Application of Cognitive Assays in Drug Development

344

(2)

Disease and Impairment Models in Drug Discovery

346

(5)

Assay and Model Validity

348

(2)

Homology between Clinical and Preclinical Measures

350

(1)

References

351

(4)

Index

355

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Animal Models of Cognitive Impairment

Summary

Table of Contents

Supplemental Materials