Front Cover

Dopamine

Copyright

Contributors

Preface

Contents

Chapter 1: Thalamostriatal synapses—another substrate for dopamine action?

1. The ``Other´´ Striatal Input

2. Thalamostriatal Targets

3. Formation and Function of Thalamostriatal Synapses

4. Impact of Thalamic Changes in Parkinson's Disease on the Motor System

5. Spine Loss in Striatal Neurons After Dopamine Removal

Acknowledgments

References

Chapter 2: Life-long consequences of juvenile exposure to psychotropic drugs on brain and behavior

1. Introduction

2. Effects of Juvenile Methylphenidate+Fluoxetine Treatment on Gene Regulation in the Striatum

2.1. Effects of Acute and Repeated MPH+FLX Treatment on Striatal IEG Expression

2.2. Effects of Acute and Repeated MPH+FLX Treatment on Striatal Neuropeptide Expression

3. Effects of Juvenile Methylphenidate+Fluoxetine Treatment on Molecular Signaling in the Midbrain and Behavior

3.1. Effects of Juvenile MPH, FLX, and MPH+FLX Exposure on Responses to Aversive Stimuli

3.2. Effects of Juvenile MPH, FLX, and MPH+FLX Exposure on ERK Signaling in the VTA

3.3. Reversal of Combined MPH+FLX-Induced Behavioral Despair in Adulthood

4. Discussion and Conclusions

Acknowledgments

References

Chapter 3: The role of learning-related dopamine signals in addiction vulnerability

1. Background

1.1. Overview

2. Model-free and Model-based Learning from Rewards

2.1. Model-Based Learning

2.2. Model-Free Prediction-Error Learning

3. Phasic Dopamine Signals Represent Model-free Prediction Errors

3.1. Causal Role of (Dopamine-Mediated) Prediction Errors in Learning

3.2. Phasic Dopamine Signals in Model-Based Learning

4. Behavioral Characteristics of Model-free and Model-based Choices

4.1. Outcome Identity

4.2. Pavlovian Approach and Consummatory Behaviors

4.3. Instrumental Behavior

4.4. Pavlovian-Instrumental Transfer (PIT)

4.5. Motivational Shifts

4.6. Unlearning

5. Individual Variability

5.1. Sign-Tracking and Goal-Tracking

5.1.1. Behavior

5.1.2. Dopamine Signals During Acquisition

5.1.3. Dopamine Signals After Acquisition

5.2. Incentive Salience Accounts of the Sign-Tracking/Goal-Tracking Variability

5.2.1. Behavior

5.2.2. Dopamine

5.3. Reinforcement Learning Accounts of the Sign-Tracking/Goal-Tracking Variability

5.3.1. Behavior

5.3.2. Dopamine Signals During Acquisition

5.3.3. Dopamine Signals After Acquisition

5.3.4. Goal-Trackers

6. Addiction

6.1. Phasic Dopaminergic Signals in Addiction

6.2. Individual Variability in Addiction Vulnerability

6.3. Shifts Toward Model-Free Learning in Addiction

6.4. Conclusions

Acknowledgments

References

Chapter 4: Dopaminergic function in relation to genes associated with risk for schizophrenia: translational mutant mouse m ...

1. Introduction

2. Mice Mutant for Dopamine-related Genes

2.1. DAergic Function and Schizophrenia

2.2. Dopamine-Releasing Drugs and Dopamine Transporter Mutants

2.3. D2 Antagonists and D2 Mutants

2.3.1. D2 KO Mutants

2.3.2. D2-Overexpressing Mutants

2.4. Overview

3. Mice Mutant for DTNBP1 (dysbindin-1)

3.1. Dysbindin-1 and Schizophrenia

3.2. Dysbindin-1 and DAergic Cell Biology

3.3. Dysbindin-1 and DAergic Function

3.4. Overview

4. Mice Mutant for NRG1/ErbB

4.1. Neuregulin-1/ErbB Signaling and Schizophrenia

4.2. Neuregulin-1/ErbB Signaling and DAergic Cell Biology

4.3. Neuregulin-1/ErbB Signaling and DAergic Function

4.3.1. Genetic Models of NRG1/ErbB Hypofunction

4.3.2. Genetic Models of NRG1/ErbB Hyperfunction

4.3.3. Nongenetic Models of NRG1/ErbB Function

4.3.4. NRG1/ErbB Involvement in Antipsychotic Action

4.4. Overview

5. Genexenvironment and Genexgene Interactions

5.1. GenexEnvironment Interactions and DAergic Function

5.2. GenexGene Interactions and DAergic Function

5.3. Overview

6. Conclusions

Acknowledgments

References

Chapter 5: Dopamine D2 heteroreceptor complexes and their receptor-receptor interactions in ventral striatum: novel target ...

1. Introduction

2. Allosteric Receptor-Receptor Interactions in Heteroreceptor Complexes

3. On the Interface of Receptor Heteromers

4. Adenosine A2AR-DA D2R Heteroreceptor Complexes

4.1. Receptor Interface

4.2. Brain Circuits and Behavioral Role

4.3. On the Possible Existence of A2A-D2-FGFR1 Heteroreceptor Complexes

5. DA D2-neurotensin NTS1 Heteroreceptor Complexes

5.1. Receptor-Receptor Interactions

5.2. Transmitter Effects In Vivo in Brain Circuits

6. DA D2-5-HT2A Heteroreceptor Complexes

6.1. RET Techniques and Proximity Ligation Assays

6.2. Signaling and Recognition

7. 5-HT2A-mGluR2 Heteroreceptor Complexes

8. D2-oxytocinR Heteroreceptor Complexes

8.1. Structure

8.2. Recognition and Signaling

9. Summary and Future Directions

Acknowledgments

References

Chapter 6: The multilingual nature of dopamine neurons

1. The Particular Nature of Dopamine Neurons

2. Discovery of cotransmitters in DA neurons

3. Localization of glutamatergic and mixed phenotype DA neurons in the brain

4. Synaptic connectivity and plasticity of glutamate release by DA neurons

5. Developmental Role of Glutamate Release by DA Neurons

6. Possible contribution of VGLUT2 in DA neurons to vesicular synergy

7. Does glutamate corelease mediate a reward-relevant signal?

Acknowledgments

References

Chapter 7: Imaging dopamine neurotransmission in live human brain

1. Molecular Imaging Techniques

2. Basic Principles and Receptor Kinetic Models

3. Single-Scan Dynamic Molecular Imaging Technique

4. Use of Multiple Kinetic Models

5. Study of Pathophysiology of Psychiatric Conditions

6. Limitations and Future Directions

7. Summary

Acknowledgments

References

Chapter 8: Dopamine receptor heteromeric complexes and their emerging functions

1. Introduction

2. The Dopamine D1 Receptor and D2 Receptor Heteromer

2.1. A Dopamine Receptor Complex Linked to Calcium Signaling

2.2. Coexpression and Interaction of D1 and D2 Dopamine Receptors

2.3. Consequences of Increased Intracellular Calcium Release

2.4. Anatomical Distribution of Neurons Expressing the D1-D2 Heteromer

2.5. Regulation of the D1-D2 Heteromer

2.6. Interaction Interface Between the D1 and D2 Receptors

3. The Dopamine D2 Receptor and Ghrelin Receptor Heteromer

3.1. GHSR1a and DRD2 Are Coexpressed in Hypothalamic Neurons Resulting in the Modification of Canonical Dopamine Signaling

3.2. GHSR1a and DRD2 Allosterically Interact via Heteromer Formation

3.3. GHSR1a:DRD2 Heteromers Regulate Food Intake

4. The Dopamine D2 Receptor and Adenosine Receptor Heteromer

4.1. Functional and Pharmacological Consequences of D2 Receptor-Containing Heteromers

4.2. Relevance of Heteromer Quaternary Structure

4.3. Presence of Heteromers in a Parkinsonian Model of Parkinson's Disease

4.4. Loss of Heteromers in l-DOPA-Induced Dyskinetic Primates

4.5. l-DOPA Treatment Disrupts A2A-CB1-D2 Receptor Heteromers

References

Chapter 9: Alcohol: mechanisms along the mesolimbic dopamine system

1. The Reward Systems in the Brain

2. The Mesolimbic Dopamine System

3. The Cholinergic-Dopaminergic Reward Link

4. Addictive Behaviors

5. The Role of Dopamine in Reward

6. The Effects of the Dopamine Stabilizer (-)-OSU6162 on Alcohol Consumption in Rodents

7. The Role of Different Reward Nodes for Alcohol Reward

8. The Role of the Cholinergic-Dopaminergic Reward Link for Reward Induced by Addictive Drugs and Behavior

9. Alcohol and Ligand-gated Ion Channels

9.1. nAChRs and Alcohol

9.2. Glycine Receptors and Alcohol

9.3. Other Ligand-Gated Ion Channels and Alcohol

10. A Possible Role of Gut-brain Peptides for Drug Dependence

10.1. The Orexigenic Peptide Ghrelin Activates the Cholinergic-Dopaminergic Reward Link

10.2. The Role for Ghrelin Signaling in Drug-Induced Reward

10.3. The Role for Glucagon-Like Peptide 1 in Drug-Induced Reward

11. Conclusions

Acknowledgments

References

Chapter 10: The role of dopamine in huntington's disease

1. Introduction

2. Striatal DA Innervation in the HD Postmortem Brain

3. Neurochemistry

4. DA Receptors

5. DA in Genetic Animal Models of HD

6. Synaptic Electrophysiology in HD Models

7. DA and Synaptic Plasticity in HD

8. DA and Excitotoxicity

9. Mechanisms of DA Dysregulation

10. DA Agonists and Antagonists as Treatments for HD

11. Conclusions and Future Directions

Acknowledgments

References

Chapter 11: Dopamine D3 receptor ligands for drug addiction treatment: update on recent findings

1. Introduction

1.1. Novel Findings Related to D3 Receptor Signaling

2. Behavioral Effects of D3 Blockade in Animal Model of Drug Addiction

2.1. Imaging D3 Receptor In Vivo

2.2. Recent Imaging Studies Using (11C)-(+)-PHNO in Drug Addiction

3. Translating the D3 Hypothesis into Clinical Intervention

4. Conclusion

References

Chapter 12: Effects of prenatal exposure to cocaine on brain structure and function

1. Introduction

2. Results

2.1. Delayed Tangential Migration of GABA Neurons Following Prenatal Cocaine Exposure

2.2. Persistent Deficits in the Numerical Density of GABA Neurons in the mPFC

2.3. BDNF: A Molecular Mediator of Cocaine's Effects on Tangential Migration of GABA Neurons

2.4. Long-Term Effects on BDNF Expression

2.5. BDNF: A Molecular Mediator of Cocaine's Effects on Cognitive Function

3. Conclusions

References

Index

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