Animal Models of Cognitive Impairment

by Levin; Edward D.

• ISBN13: 9780849328343
• ISBN10: 0849328349
• Edition: 1st
• Format: Hardcover
• Copyright: 2006-06-22
• Publisher: CRC Press

Summary

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.

Table of Contents

Chapter 1 Introduction	1	(4)
Edward D. Levin and Jerry J. Buccafusco
SECTION I Pharmacologic Models
Chapter 2 Muscarinic Receptor Antagonists in Rats	5	(16)
Alvin V. Terry, Jr.
Introduction	5	(1)
Memory-Related Task Impairment in Rats by Scopolamine and Other Antimuscarinic Agents	6	(2)
The Nature of the Effects of Antimuscarinics on Memory Performance (Potential Limitations)	8	(1)
Other Limitations and Criticisms of the Use of Antimuscarinics as Amnestic Agents	9	(3)
Scopolamine-Reversal Studies and Drug Discovery	12	(2)
Conclusions	14	(1)
References	14	(7)
Chapter 3 Nicotinic Receptor Antagonists in Rats	21	(16)
Cindy S. Roegge and Edward D. Levin
Introduction	21	(1)
Radial Arm Maze (RAM)	22	(2)
Three-Panel Runway Task	24	(1)
T-Maze Alternation	25	(1)
T-Maze Discrimination	25	(1)
Delayed (Non)Matching to Sample	25	(3)
Tests of Sustained Attention	28	(1)
Tests of Response Inhibition	28	(1)
Water Maze	29	(1)
Avoidance Learning	30	(2)
Conclusions	32	(1)
References	32	(5)
Chapter 4 Involvement of the NMDA System in Learning and Memory	37	(12)
Amir H. Rezvani
Introduction	37	(1)
Animal Studies	37	(5)
NMDA	38	(1)
Transgenic and Mutant Mice	38	(1)
NMDA Antagonists	39	(3)
NMDA Transporter Inhibitors	42	(1)
Human Studies	42	(2)
Conclusions	44	(1)
References	44	(5)
Chapter 5 Animal Models and the Cognitive Effects of Ethanol	49	(24)
Merle G. Paule
Background	49	(2)
Behavioral Effects in Animal Models	51	(13)
Relevance	51	(1)
Mechanism(s) of Action of Ethanol	51	(1)
Subjective Effects: Drug Discrimination Studies	51	(6)
Effects of Ethanol on Other Aspects of Cognition: Attention, Learning, and Memory	57	(1)
Attention/Impulsivity	57	(1)
Conditioning	58	(1)
Learning and Memory	59	(1)
Working/Short-Term Memory	59	(3)
Comparative Sensitivities of Different Cognitive Functions to the Effects of Ethanol	62	(1)
Age-Related Differences in Sensitivity to Ethanol	63	(1)
Environmental and Other Influences on the Effects of Ethanol	63	(1)
Overview	64	(1)
References	64	(9)
SECTION II Toxicologic Models
Chapter 6 Animal Models of Cognitive Impairment Produced by Developmental Lead Exposure	73	(28)
Deborah C. Rice
Intermittent Schedules of Reinforcement	74	(3)
Learning	77	(6)
Memory	83	(6)
Attention	89	(3)
Sensory Dysfunction: Possible Contribution to "Cognitive" Effects	92	(2)
Conclusions	94	(1)
References	95	(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