Chapter

METABOTROPIC GLUTAMATE RECEPTORS: MOLECULAR MECHANISMS, ROLE IN NEUROLOGICAL DISORDERS AND PHARMACOLOGICAL EFFECTS

METABOTROPIC GLUTAMATE RECEPTORS: MOLECULAR MECHANISMS, ROLE IN NEUROLOGICAL DISORDERS AND PHARMACOLOGICAL EFFECTS

Library of Congress Cataloging-in-Publication Data

Contents

Preface

Chapter 1: Brainstem Metabotropic Glutamate Receptors and Regulation of Autonomic Responses

Abstract

Introduction

Metabotropic Glutamate Receptors and Brainstem Cardiovascular Functions

Metabotropic Glutamate Receptors and Brainstem Respiratory Functions

Role of Metabotropic Glutamate Receptors in the Defensive Behaviour

Metabotropic Glutamate Receptors as a Potential Drug Target for the Therapy of Diseases

Conclusion

References

Chapter 2: Activation of Group I Metabotropic Glutamate Receptors Negatively Regulates Synaptic Plasticity and Network Activity in the Central Nervous System via Inositol 1,4,5-Trisphosphate Receptor Signaling

Abstract

1. Metabotropic Glutamate Receptors in Neurons

2. Metabotropic Glutamate Receptors, NMDA Receptors, and Synaptic Plasticity

3. Activation of mGluRs Reverses LTP(Depotentiation)

4. mGluR Activation Inhibits Certain Forms of LTP(Suppression of LTP)

5. Negative Regulatory Effect of mGluR-IP3RSignaling in Synaptic Plasticity

7. LTP and LTD May Involve Both Facilitatory andInhibitory Changes and the Direction andAmplitude of Synaptic Plasticity Is Determined bythe Balance of Facilitatory and InhibitoryMechanisms Downstream of Receptor Activation

8. mGluR-IP3R Signaling Acts as a NegativeRegulator of LTP and Stabilizes Network Activity

References

Chapter 3: Group I mGluR Receptors as Mediators of Learning and Memory

Abstract

Introduction

Signaling Mechanisms of Group I mGluRs

Group I mGluRs and Synaptic Plasticity

Inhibitory Effects of Group I mGluRInactivation on Learning and Memory

Facilitatory Effects of Group I mGluRActivation on Learning and Memory

Conclusion

References

Chapter 4: Group I Metabotropic Glutamate Receptors: A Potential Therapeutic Target for Amyloidogenic Disorders

Abstract

Introduction

Molecular Mechanisms Underlying AbPP Synthesis and Processing

Roles of AbPP Catabolites and mGluR5 in Neurological Disorders

Therapeutic Approaches to Modulate AbPP and Ab

Conclusion

References

Chapter 5: Metabotropic Glutamate Receptors in the Pathophysiology and Treatment of Schizophrenia and Major Depression

Abstract

Introduction

mGluRs in the Pathophysiology of Schizophrenia and Major Depression

The Effects of Current Antipsychotic Therapeutics on mGluRs

The Effects of Current Antidepressant Therapeutics on mGluRs

mGluRs as Novel Therapeutic Targets for Schizophrenia and Major Depression

Conclusion

Acknowledgments

References

Chapter 6: Metabotropic Glutamate Receptor Subtype 1 (mGluR1) as a Therapeutic Target for Schizophrenia

Abstract

Abbreviations

Introduction

Development of mGluR1-Selective NAMs

In Vivo Measurement of mGluR1 Activity and Receptor Occupancy

mGluR1 As a Therapeutic Target for Schizophrenia

Profiling of mGluR1 Blockade by Fos Expression Pattern

Potential Adverse Effects of mGluR1 Blockade

Further Development of mGluR1 NAMs and Biomarkers for Proof-of-Concept

Conclusion

Acknowledgments

References

Chapter 7: Group I and Group II Metabotropic Glutamate Receptors: Role in Pathophysiology and Treatment of Major Depressive Disorder

Abstract

Introduction

Glutamate Dysfunction in MDD

Glutamate and mGluR Physiology

Animal Models of Depression

Disruptions in the mGluR System as a Consequence of Animal Models of Depression

Disruptions in the mGluR System as a Consequence of Chronic Antidepressant Administration

Antidepressant Actions of Drugs that Target mGluRs

Conclusion

References

Chapter 8: Involvement of mGluR5 and mGluR2/3in Drug and Alcohol Dependence

Abstract

Introduction

Cocaine

Nicotine

Opioids

Ethanol

Conclusion

Acknowledgments

References

Chapter 9: Therapeutic Potential of mGluR Agents on Substance Abuse and Mood Disorders: Role of Stress Reactivity during Abstinence and Withdrawal

Abstract

Introduction

The Roles of mGluRs in the Progressive Stages of Addiction

Physiology of Stress Systems

mGluR Agents and Stress- and Anxiety-Related Behaviors

Withdrawal-Induced Stress and Anxiety: Therapeutic Potential of mGluR Agents

Conclusion

References

Index