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9. REPAIRING THE FRAGILE SYNAPSE 452

9.1. MPEP and Other MGluR Antagonists 452

9.3. Gene Therapy 453

9.4. Other Options 453

10. CONCLUSIONS 454

11. REFERENCES 454

Chapter 31: SYNAPTIC ABNORMALITIES ASSOCIATED WITH HUNTINGTON'S DISEASE, Austen J. Milnerwood and Lynn A. Raymond 457

1. SUMMARY 457

2. INTRODUCTION TO HD 457

3. SELECTIVE NEURONAL VULNERABILITY IN HD 458

4. PRESYNAPTIC DYSFUNCTION 459

4.1. Axonal Transport 459

4.2. Vesicle Fusion and Neurotransmitter Release 460

4.3. Vesicle Recovery 461

4.4. Glutamate Uptake 461

4.5. Presynaptic Dysfunction and HD Symptom Progression 461

5. POSTSYNAPTIC DYSFUNCTION 462

5.1. Morphological and Gross Membrane Alterations 462

5.2. Excitotoxicity and Glutamate Receptor Function 462

5.3. NMDA Receptor Trafficking and Surface Expression 464

5.4. Dopamine Receptor Signaling 465

5.5. GABA Receptors and Signaling 466

6. SYNAPTIC PLASTICITY AND COGNITIVE FUNCTION 466

7. CONCLUSIONS 467

8. REFERENCES 469

Chapter 32: INTERFERENCE PEPTIDES: A NOVEL THERAPEUTIC APPROACH TARGETING SYNAPTIC PLASTICITY IN DRUG ADDICTION, Karen Brebner, Anthony G. Phillips, Yu Tian Wang, and Tak Pan Wong 473

1. SUMMARY 473

2. INTRODUCTION 473

3. LTD AND BEHAVIORAL SENSITIZATION: A MODEL FOR THE ROLE OF SYNAPTIC PLASTICITY IN ADDICTION 475

4. GLUTAMATERGIC INVOLVEMENT IN SYNAPTIC PLASTICITY ...476

5. AMPAR ENDOCYTOSIS IN LTD 476

6. POTENTIAL UTILITY OF INTERFERENCE PEPTIDES IN THE TREATMENT OF DRUG ADDICTION LTD 479

7. CONCLUSIONS 482

8. REFERENCES 483

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