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Preface -- Contents -- Chapter 1: mGlu5 Signaling: A Target for Addiction Therapeutics? -- 1.1 Introduction: Pharmacotherapy and Allosteric Modulators -- 1.2 Negative Allosteric Modulators Reduce Drug Reward -- 1.3 mGlu5 Receptors and Synaptic Plasticity -- 1.4 mGlu5 Receptor Expression Changes Across Development of Addiction -- 1.5 Cognitive Capacity Is Positively Correlated with Treatment Outcome for Substance Abuse Disorders -- 1.6 Amnestic Effects of mGlu5 Inactivation -- 1.7 Facilitatory Effects of mGlu5 Activation on Learning, Memory, and Extinction Processes -- 1.8 Conclusion -- References -- Chapter 2: Supraspinal Metabotropic Glutamate Receptors: An Endogenous Substrate for Alleviating Chronic Pain and Related Affective Disorders -- 2.1 Introduction -- 2.2 mGluRs and Pain Processing -- 2.3 Group I mGluRs -- 2.4 Group II mGluRs -- 2.5 Group III mGluRs -- 2.6 Conclusion -- References -- Chapter 3: Metabotropic Glutamate Receptors and Parkinson's Disease: Basic and Preclinical Neuroscience -- 3.1 Parkinson's Disease -- 3.2 Rationale for Targeting mGlu Receptors for Parkinson's Disease -- 3.3 Localization and Function of mGlu Receptors in the Basal Ganglia -- 3.3.1 Group I mGlu Receptors -- 3.3.2 Group II mGlu Receptors -- 3.3.3 Group III mGlu Receptors -- 3.4 Group I mGlu Receptors and Parkinson's Disease -- 3.5 Group II mGlu Receptors and Parkinson's Disease -- 3.6 Group III mGlu Receptors and Parkinson's Disease -- 3.7 Concluding Remarks -- References -- Chapter 4: Metabotropic Glutamate 2 (mGlu2) Receptors and Schizophrenia Treatment -- 4.1 Schizophrenia -- 4.2 Metabotropic Glutamate Receptors -- 4.3 Preclinical and Clinical Schizophrenia Assays with mGlu2/3 Receptor Agonists -- 4.4 Environmental Events and mGlu2 Expression -- 4.5 Expression of mGlu2 and 5-HT2A as a GPCR Heteromer in Schizophrenia Treatment -- 4.6 Conclusions
References -- Chapter 5: mGlu5: A Metabotropic Glutamate Receptor at the Hub of Hippocampal Information Processing, Persistent Synaptic Plasticity, and Long-Term Memory -- 5.1 Introduction -- 5.2 Role of mGlu5 in Persistent Forms of Hippocampal Synaptic Plasticity and Memory -- 5.2.1 Role of mGlu5 in Persistent LTP and LTP-Related Memory -- 5.2.2 Role of mGlu5 in Persistent LTD and LTD-Related Memory -- 5.3 Role of mGlu5 in Hippocampal Information Processing -- 5.3.1 Neuronal Oscillations -- 5.3.2 The Role of mGlu5 in Place Fields -- 5.3.3 The Special Case of the CA3 Region -- 5.4 mGlu5 at the Hub of Hippocampal Function -- References -- Chapter 6: Neuroprotective Properties of Glutamate Metabotropic Glutamate Receptors in Parkinson's Disease and Other Brain Disorders -- 6.1 Introduction -- 6.2 MGluR Localization in the Basal Ganglia Circuitry -- 6.3 Neuroprotective Effects of Group I mGluRs -- 6.4 Neuroprotective Effects of Group II mGluRs in PD -- 6.5 Neuroprotective Effects of Group III mGluRs in PD -- 6.6 Neuroprotective Effects of mGluR-Related Drugs in Other Brain Diseases -- 6.7 Anti-inflammatory Properties of mGluRs: Implications for Neuroprotection -- 6.8 mGluR-Mediated Neuroprotection vs Disease Biomarkers -- References -- Chapter 7: Structure, Dynamics, and Modulation of Metabotropic Glutamate Receptors -- 7.1 Introduction -- 7.2 Functional Organization and Structure of the mGluRs -- 7.3 Crystal Structures and Conformational States of the mGluR -- 7.4 Structural Dynamics of the mGluR ECD During Activation -- 7.5 Dynamics of the mGluR Transmembrane Domain During Activation -- 7.6 Molecular Bases of Ligand Efficacy: Partial Agonism -- 7.7 Allosteric Modulation of the mGluRs -- 7.8 Innovative Ligands Control the Activity of mGluRs with Light -- 7.9 Conclusion and Future Perspectives -- References
Chapter 8: Metabotropic Glutamate Receptor Function in Thalamocortical Circuitry -- 8.1 Introduction -- 8.2 The Thalamus -- 8.3 Localisation of mGlu Receptors in Thalamocortical Circuitry -- 8.3.1 Group I Receptors -- 8.3.2 Group II Receptors -- 8.3.3 Group III Receptors -- 8.4 mGlu Function in Thalamocortical Circuitry in Health and Disease -- 8.5 Summary -- References -- Chapter 9: Metabotropic Glutamate Receptors in Cancer -- 9.1 Glutamine and Glutamate -- 9.2 mGluRs in Cancer -- 9.3 mGluRs in Primary Brain Tumors -- 9.4 mGluRs in Non-neuronal Cancers -- 9.5 mGluR1 in Melanoma -- 9.6 mGluR1 as a Therapeutic Target in Treating Melanoma -- 9.7 mGluR1 in Brain Metastasis -- 9.8 mGluR1 in Breast Cancer -- 9.9 Conclusions -- References -- Chapter 10: mGlu5 Receptors in Parkinson's Disease and MPTP-Lesioned Monkeys: Behavior and Brain Molecular Correlates -- 10.1 Introduction -- 10.2 Nonhuman Primate Models of L-DOPA-Induced Dyskinesias -- 10.3 Glutamate Neurotransmission in PD and L-DOPA-Induced Dyskinesias -- 10.4 Ionotropic Glutamate Receptors and L-DOPA-Induced Dyskinesias -- 10.5 Metabotropic Glutamate Receptors and L-DOPA-Induced Dyskinesias -- 10.6 The Effect of a Chronic Treatment with MPEP on L-DOPA-Induced Dyskinesias and Brain Biochemical Borrelates -- 10.7 Conclusion -- References -- Chapter 11: Is There a Future for mGlu5-Positive Allosteric Modulators in Absence Epilepsy? A Comparison with Ethosuximide -- 11.1 Introduction -- 11.2 The Assumed Working Mechanisms of ETX -- 11.3 New Anti-absence Drugs -- 11.4 Neurochemical Studies -- 11.5 Acute and Subchronic Pharmacological Studies -- 11.6 Local Injection Studies -- 11.7 Comparison Between Ethosuximide and VU0360172 -- 11.8 Discussion -- References -- Chapter 12: Regulation of Hippocampal mGluR-Dependent Long-Term Depression by GluA2-Dependent Cofilin-Mediated Actin Remodeling
12.1 Introduction -- 12.2 AMPA Glutamate Receptors Mediate Synaptic Plasticity -- 12.3 Rho Signaling Pathways Mediate Spine Plasticity -- 12.4 Cofilin Regulates Spine Actin and Basal Spine Morphology -- 12.5 Cofilin Regulates Both Spine Plasticity and mGluR-LTD -- 12.6 GluA2 Is Necessary for mGluR-LTD and Associated Spine Plasticity -- 12.7 GluA2 Regulation of mGluR-LTD and Spines Is Mediated by Cofilin -- 12.8 GluA2 Regulates Cofilin Through Its N-terminal Interaction with N-cadherin and Subsequent Activation of Rac1 -- 12.9 Concluding Remarks and Future Studies -- References -- Chapter 13: Metabotropic Glutamate Receptors in Amygdala Functions -- 13.1 Introduction -- 13.2 Basic Anatomical Organization of the Amygdala -- 13.3 Historical Overview -- 13.4 Distribution of mGluRs in the Amygdala -- 13.5 Expression of Group I mGluRs in Amygdala -- 13.6 Expression of Group II mGluRs in Amygdala -- 13.7 Expression of Group III mGluRs in Amygdala -- 13.8 Physiology -- 13.9 Relevance of mGluRs for Amygdala-Dependent Emotional Behaviours -- 13.10 Role of mGluRs in Fear Learning -- 13.11 Influence of Group I mGluRs on Fear Learning -- 13.12 Influence of Group II mGluRs on Fear Learning -- 13.13 Influence of Group III mGluRs on Fear Learning -- 13.14 Role of mGluRs in Social Behaviours -- 13.15 Relevance of Amygdala mGluRs for Human Neuropsychiatric Disorders -- 13.16 Anxiety Disorders -- 13.17 Modulation of Anxiety-Like Behaviours by Group I mGluRs -- 13.18 Modulation of Anxiety-Like Behaviours by Group II mGluRs -- 13.19 Modulation of Anxiety-Like Behaviours by Group III mGluRs -- 13.20 Influence of Amygdala mGluRs on Addiction -- 13.21 Role of Amygdala mGluRs on Emotional-Affective Dimensions of Pain -- 13.22 Role of Amygdala mGluRs on Sleep Disorders -- 13.23 Autism Spectrum Disorders -- 13.24 Conclusions -- References -- Index
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