It has been almost forty years since Norman G. Bowery discovered and named this “non-GABAA” receptor the GABAB receptor. It has been almost ten years since the last comprehensive book presentation focused on GABAB receptors.
The main goal of this book is to provide the field with a contemporary and comprehensive perspective on the GABAB receptor, its physiological relevance, and its therapeutic potential. The volume is organized into introductory and special interest sections presented by experts who study the GABAB receptor from structural, signaling, pharmacologic, physiological, pathophysiological, and therapeutic perspectives.
The book aims to appeal to a broad spectrum of biomedical and clinical scientists - any scholars with an interest in GABAB receptor. The editors hope readers find this work to be thought-provoking, instructive, and informative..
Author(s): Styliani Vlachou, Kevin Wickman
Series: Current Topics in Behavioral Neurosciences, 52
Publisher: Springer
Year: 2022
Language: English
Pages: 329
City: Cham
Preface
Contents
A Brief History and the Significance of the GABAB Receptor
1 Introduction
2 GABAB Receptor Structure, Function, and Distribution
3 GABAB Receptor Ligands: Agonists, Antagonists, and Allosteric Modulators
4 GABAB Receptors as Potential Therapeutic Targets
4.1 Drug and Alcohol Use Disorders
4.2 Pain and Analgesia
4.3 Anxiety and Mood Disorders
4.4 Neurodegeneration
4.5 Cognitive Processes in Neurodevelopment, Health and Disease
4.6 Other Conditions Outside the CNS
5 Conclusion
References
Structural Basis of GABAB Receptor Regulation and Signaling
1 Heterodimers Are the Minimal Functional Receptor Units
2 Signal Transduction in the Receptor Heterodimer
3 Auxiliary KCTD Subunits
4 SD-Interacting Proteins
5 Effector Channels
6 Additional Receptor-Associated Proteins
7 Concluding Remarks
References
Mechanisms and Regulation of Neuronal GABAB Receptor-Dependent Signaling
1 Introduction
2 GABABR Structure
2.1 Ligand Binding
2.2 Coupling to G Proteins
2.3 Cell Surface Trafficking
2.4 Alternative Splicing
2.5 Oligomerization
2.6 GABABR Signalosome
3 GABABR-Dependent Signaling in Neurons
3.1 GABABR Coupling to G Proteins
3.2 GABABR Regulation of Effectors
3.2.1 GIRK Channels
3.2.2 Voltage-Gated Ca2+ Channels
3.2.3 Adenylyl Cyclase
4 Regulation of GABABR-Dependent Signaling in Neurons
4.1 Desensitization
4.2 Phosphorylation
4.2.1 CaMKII
4.2.2 AMPK
4.2.3 PKA
4.2.4 PKC
4.3 Ubiquitination
4.4 KCTD Proteins
4.5 RGS Proteins
4.5.1 R7 RGS/Gβ5
4.5.2 R4 RGS Proteins
4.5.3 RGS12
5 Plasticity of GABABR-Dependent Signaling
5.1 Phosphorylation-Dependent Plasticity
5.2 Plasticity of 14-3-3 Proteins
5.3 Plasticity of RGS Regulation
6 Concluding Remarks
References
GABAB Receptor Chemistry and Pharmacology: Agonists, Antagonists, and Allosteric Modulators
1 Introduction
2 Brief History
3 Structure and Signaling
4 Molecular Diversity and Complexity
5 Agonists
6 Partial Agonists
7 Antagonists
8 Inverse Agonists
9 Allosteric Modulators
10 Probe Dependency
11 Biased Agonism/Functional Selectivity
12 GABAB Receptor-Targeted Pharmaceuticals
13 Concluding Remarks
References
GABAB Receptors and Drug Addiction: Psychostimulants and Other Drugs of Abuse
1 Introduction
2 GABABR Signaling in the Reward Circuit
2.1 The VTA Microcircuit
2.2 GABAergic Inputs to the VTA
3 Impact of Addictive Drugs on GABABR Signaling in the Reward Circuit
3.1 Psychostimulants
3.2 Nicotine
3.3 Opioids
3.4 Cannabis
3.5 Summary
4 Effects of Genetic Manipulations of GABABR on Animal Models of Drug Addiction
5 Effects of Pharmacological Manipulations on Animal Models of Drug Addiction: Agonists, Antagonists, and Positive Allosteric ...
5.1 Psychostimulants
5.1.1 Amphetamine and Methamphetamine
5.1.2 Cocaine
5.2 Nicotine
5.3 Opioids
5.4 Other Drugs/Reinforcers
5.5 Stress and Addiction
5.6 Summary
6 Clinical Studies of GABABR Modulators in Drug Addiction
7 Conclusions
References
GABAB Receptors and Alcohol Use Disorders: Preclinical Studies
1 GABAB Receptors and Alcohol Use Disorders: Preclinical Studies
2 Locomotor Activity
3 Place Conditioning
4 Alcohol Withdrawal Syndrome
5 Alcohol Drinking
5.1 Acquisition and Maintenance of Alcohol Drinking
5.2 Binge-Like Drinking
5.3 Relapse-Like Drinking
6 Operant Alcohol Self-Administration
6.1 Fixed Ratio (FR) Procedure
6.2 Progressive Ratio (PR) Procedure
6.3 Extinction and Reinstatement of Alcohol Seeking Procedures
6.4 Appetitive-Consummatory Procedures
7 Discussion
References
GABAB Receptors and Alcohol Use Disorders: Clinical Studies
1 Introduction
2 Overview of Pharmacotherapies Modulating the GABAB Receptor
2.1 Baclofen
2.2 γ-Hydroxybutyric Acid
3 Treatment for Alcohol Withdrawal Syndrome
4 Relapse Prevention in Alcohol Use Disorders
4.1 Baclofen: Low-to-Moderate Doses
4.2 Baclofen: High-Doses
4.3 Specific Populations
4.3.1 Alcohol-Related Liver Disease
4.3.2 Comorbid Anxiety
5 Meta-Analyses Assessing Baclofen´s Efficacy
6 Laboratory Studies Evaluating Craving and Biobehavioural Effects of Baclofen
6.1 Functional Brain Activation Correlates with Baclofen
7 Polymorphisms Associated with Baclofen Treatment Response
8 Safety Concerns with Baclofen
9 Conclusions
References
GABAB Receptors and Pain
1 Introduction
1.1 Pain-Related Terminology
2 Expression and Function of GABAB Receptors in Nociceptive Pathways
2.1 GABAB Receptors in Nociceptors
2.1.1 GABAB Receptors in Peripheral Axon Endings of Nociceptors
2.1.2 GABAB Receptors in Central Axon Endings of Nociceptors
2.2 GABAB Receptors in Dorsal Horn Interneurons and Projection Neurons
2.3 GABAB Receptors in Supraspinal Areas
2.4 GABAB Receptors in Descending Pain Control Pathways
3 GABAB Receptors and Pathological Pain
3.1 GABAB Receptors and Inflammatory Pain
3.2 GABAB Receptors and Neuropathic Pain
4 GABAB Receptors as Target for Treating Chronic Pain
5 Conclusions
References
GABAB Receptors: Anxiety and Mood Disorders
1 Introduction
2 Role of the GABAB Receptor in the Modulation of Anxiety
2.1 Effects of GABAB Receptor Agonists and Positive Allosteric Modulators on Anxiety-Like Behaviour
2.2 Effects of GABAB Receptor Loss of Function and GABAB Receptor Antagonists on Anxiety-Like Behaviour
3 Role of the GABAB Receptor in Depression and Antidepressant Action
3.1 Effects of GABAB Receptor Agonists on Depression-Like Behaviour
3.2 Effects of GABAB Receptor Blockade or Loss of Function on Depression-Like Behaviour
4 Clinical Evidence of the Role of GABAB Receptor in Mood Disorders
5 Conclusions and Perspectives
References
GABAB Receptors in Neurodegeneration
1 Introduction
2 GABAB Receptor and Its Effects
2.1 K+ Channels
2.2 Ca2+ Channels
2.3 Inhibition of Adenylate Cyclase
3 GABAA Receptors
4 GABAB in Neurodegenerative Diseases
4.1 GABAB in Alzheimer´s Disease
4.2 GABAB in Parkinson´s Disease
4.3 GABAB in Temporal Lobe Epilepsy
5 Conclusions
References
GABAB Receptors and Cognitive Processing in Health and Disease
1 Introduction
2 GABAB Receptors Mechanisms of Action
3 Effects of GABAB Receptors on Cognitive Processes: Learning and Memory
3.1 GABAB Receptors, LTP and Synaptic Plasticity
3.2 Active and Passive Avoidance Paradigms
3.3 Morris Water Maze (MWM) and Radial Arm Maze (RAM)
3.4 Working Memory Tasks
3.5 Novel-Object Recognition (NOR) and (Dis)Location (NOL) Tasks
3.6 Other Cognitive Tasks
4 GABABR Involvement in Cognitive Performance of Neurodevelopmental Conditions
4.1 GABABRs During Embryo-Foetal Development
4.2 Autism Spectrum Disorder (ASD)
4.3 Fragile X Syndrome (FXS)
4.4 Down´s Syndrome (DS)
5 Neurodegenerative Disorders
5.1 Alzheimer´s Disease (AD)
5.2 Epilepsy
5.3 Autoimmune Anti-GABAB Encephalitis and Cognitive Impairments
6 Conclusions
References
