Ho Man Choi. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (leaves 178-215). / Abstracts and appendices in English and Chinese. / ACKNOWLEDGEMENT --- p.ii / ABSTRACT --- p.iii / 研究摘要 --- p.vi / Chapter CHAPTER 1 --- INTRODUCTION / Chapter 1.1. --- Heroin --- p.1 / Chapter 1.1.1. --- Manufacture --- p.1 / Chapter 1.1.2. --- Administration --- p.2 / Chapter 1.1.3. --- Physical and Psychological Effects --- p.4 / Chapter 1.1.4. --- Heroin Metabolism --- p.5 / Chapter 1.1.5. --- Treatments for Heroin Dependence --- p.6 / Chapter 1.2. --- Opioids and Analgesia --- p.8 / Chapter 1.2.1. --- Pain Transmission --- p.8 / Chapter 1.2.2. --- Pain Modulation and Endogenous Opioid System --- p.9 / Chapter 1.2.3. --- Clinical Application of Opiates in Pain Management --- p.11 / Chapter 1.2.4. --- Narcotics and Pain --- p.11 / Chapter 1.3. --- Biological Basis of Drug Addiction --- p.12 / Chapter 1.3.1. --- Mesocorticolimbic Reward System --- p.13 / Chapter 1.3.2. --- Molecular Neurobiology of Drug Addiction --- p.16 / Chapter 1.3.2.1. --- "Cyclic Adenosine-3',5'-Monophosphate and Protein Kinase A" --- p.16 / Chapter 1.3.2.2. --- Transcription Factors: cAMP-Response Element Binding Protein and Delta-Fos B --- p.18 / Chapter 1.3.2.3. --- Neurotrophic Factors --- p.23 / Chapter 1.4. --- Biological Basis of Relapse --- p.25 / Chapter 1.4.1. --- Environmental Stimuli --- p.26 / Chapter 1.4.2. --- Drug Re-exposure/Priming --- p.26 / Chapter 1.4.3. --- Acute Stress Exposure --- p.27 / Chapter 1.5. --- Gene Polymorphisms and Opioid Dependence --- p.30 / Chapter 1.5.1. --- Opioidergic System --- p.31 / Chapter 1.5.2. --- Dopaminergic System --- p.36 / Chapter 1.5.3. --- Serotoninergic System --- p.41 / Chapter 1.5.4. --- Noradrenergic System --- p.43 / Chapter 1.5.5. --- GABAergic System --- p.44 / Chapter 1.6. --- Aim of Research --- p.45 / Chapter CHAPTER 2 --- METHODS OF STUDY / Chapter 2.1. --- Subject Recruitment and Demographic Data Collection --- p.49 / Chapter 2.1.1. --- Heroin-dependent Subjects --- p.49 / Chapter 2.1.1.1. --- Phenotype Assessment --- p.49 / Chapter 2.1.1.2. --- Socio-demographics Data and Substance Use History --- p.50 / Chapter 2.1.1.3. --- Addiction Severity Index (ASI) --- p.51 / Chapter 2.1.1.4. --- History of Detoxifications and Relapse --- p.51 / Chapter 2.1.2. --- Control Subjects --- p.51 / Chapter 2.2. --- Pain Response Assessment using Cold-Pressor Test (CPT) --- p.52 / Chapter 2.3. --- Personality Trait Assessment --- p.53 / Chapter 2.4. --- Genotype Analysis --- p.55 / Chapter 2.4.1. --- DNA Extraction --- p.55 / Chapter 2.4.2. --- Genotyping --- p.56 / Chapter 2.4.2.1. --- MORA118G --- p.56 / Chapter 2.4.2.2. --- DOR T921C --- p.56 / Chapter 2.4.2.3. --- COMTVal108/158Met --- p.57 / Chapter 2.4.2.4. --- Prodynorphin 68bp-VNTR --- p.58 / Chapter 2.4.2.5. --- DRD2 TaqI A --- p.59 / Chapter 2.4.2.6. --- DRD4 -521C/T --- p.59 / Chapter 2.4.2.7. --- 5HT1B G861C --- p.60 / Chapter 2.5. --- Saliva Collection and Salivary Cortisol Measurement --- p.61 / Chapter 2.6. --- Statistical Analysis --- p.62 / Chapter CHAPTER 3 --- RESULTS / Chapter 3.1. --- Demographics --- p.64 / Chapter 3.1.1. --- Age --- p.64 / Chapter 3.1.2. --- Ethnicity --- p.64 / Chapter 3.1.3. --- District of Residence and Type of Housing --- p.64 / Chapter 3.1.4. --- "Education, Employment and Income" --- p.68 / Chapter 3.1.5. --- ASI Scores --- p.71 / Chapter 3.1.5.1. --- Family/Social Relationship --- p.71 / Chapter 3.1.5.2. --- Employment and Support Status --- p.73 / Chapter 3.1.5.3. --- Medical Status --- p.73 / Chapter 3.1.5.4. --- Legal Status --- p.75 / Chapter 3.1.5.5. --- Psychiatric Status --- p.75 / Chapter 3.1.5.6. --- Drug Use Status --- p.76 / Chapter 3.1.5.7. --- Alcohol Use Status --- p.79 / Chapter 3.1.6. --- Tranquillizer Use Status --- p.79 / Chapter 3.1.7. --- Smoking Status --- p.81 / Chapter 3.1.8. --- Detoxification and Relapse --- p.83 / Chapter 3.2. --- Cold-Pressor Test (CPT) --- p.88 / Chapter 3.3. --- Personality Traits --- p.90 / Chapter 3.3.1. --- NEO PI-R --- p.90 / Chapter 3.3.2. --- BIS/BAS --- p.93 / Chapter 3.3.3. --- SSS-V --- p.93 / Chapter 3.4. --- Salivary Cortisol Levels --- p.93 / Chapter 3.5. --- Genotype and Allele Frequencies of Gene Polymorphisms --- p.96 / Chapter 3.5.1. --- MOR A118G Polymorphism --- p.96 / Chapter 3.5.2. --- DOR T921C Polymorphism --- p.96 / Chapter 3.5.3. --- COMT Val108/158Met Polymorphism --- p.99 / Chapter 3.5.4. --- Prodynorphin 68bp-VNTR --- p.99 / Chapter 3.5.5. --- DRD2 TαqI A Polymorphism --- p.102 / Chapter 3.5.6. --- DRD4 -521C/T Polymorphism --- p.102 / Chapter 3.5.7. --- 5HT1B G861C Polymorphism --- p.105 / Chapter 3.6. --- "Association of Gene Polymorphisms, Personality Traits and CPT" --- p.105 / Chapter 3.7. --- Association of Gene Polymorphisms and CPT --- p.108 / Chapter 3.7.1. --- COMT Val108/158Met Polymorphism --- p.108 / Chapter 3.7.2. --- DRD4 -521C/T Polymorphism --- p.108 / Chapter CHAPTER 4 --- DISCUSSIONS AND CONCLUSIONS / Chapter 4.1. --- Demographics and Potential Environmental Factors of Relapse --- p.111 / Chapter 4.1.1. --- Medical and Psychological Status --- p.114 / Chapter 4.1.2. --- Substance Use Status --- p.116 / Chapter 4.1.3. --- Detoxification and Relapse --- p.118 / Chapter 4.2. --- Cold-Pressor Test (CPT) --- p.121 / Chapter 4.3. --- Personality Traits --- p.123 / Chapter 4.4. --- Salivary Cortisol --- p.125 / Chapter 4.5. --- "Association of Gene Polymorphisms, Personality Traits and Cold-Pressor Test" --- p.127 / Chapter 4.5.1. --- MORA118G Polymorphism --- p.127 / Chapter 4.5.2. --- DOR T921C Polymorphism --- p.129 / Chapter 4.5.3. --- COMT Val108/158Met --- p.130 / Chapter 4.5.4. --- Prodynorphin (ProDYN) 68bp-VNTR --- p.133 / Chapter 4.5.5. --- DRD2 A Polymorphism --- p.134 / Chapter 4.5.6. --- DRD4 -521C/T Polymorphism --- p.138 / Chapter 4.5.7. --- 5HTlB G861C Polymorphism --- p.141 / Chapter 4.5.8. --- Personality Traits --- p.142 / Chapter 4.6. --- Limitations --- p.144 / Chapter 4.7. --- Potential Clinical Application --- p.145 / Chapter 4.8. --- Conclusion --- p.146 / APPENDIXES --- p.148 / APPENDIX 1 Addiction Severity Index (ASI) with Additional Questions for Heroin Users / APPENDIX 2 Detoxification and Relapse History Questionnaire / APPENDIX 3A Questionnaire for Control Subjects (Chinese version) / APPENDIX 3B Questionnaire for Control Subjects (English version) / APPENDIX 4A NEO PI-R (Chinese version) / APPENDIX 4B NEO PI-R (English version) / APPENDIX 5A BIS/BAS (Chinese version) / APPENDIX 5B BIS/BAS (English version) / APPENDIX 6A SSS- V (Chinese version) / APPENDIX 6B SSS- V (English version) / REFERENCES --- p.178

Szeto Yi Ki. / Thesis submitted in: December 2000. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (leaves 83-113). / Abstracts in English and Chinese. / Acknowledgement --- p.iv / Abstract --- p.v / List of Abbreviations --- p.ix / Chapter CHATPER ONE --- INTRODUCTION / Chapter 1.1 --- Heroin --- p.1 / Chapter 1.1.1 --- Historical Background --- p.2 / Chapter 1.1.2 --- Manufacturing of Heroin --- p.5 / Chapter 1.1.3 --- Route of Administration and Absorption Rate --- p.6 / Chapter 1.1.4 --- Metabolism of Heroin --- p.8 / Chapter 1.1.5 --- Physical and Psychological Effects of Heroin --- p.9 / Chapter 1.2 --- Opioid Receptors --- p.10 / Chapter 1.2.1 --- Mu Opioid Receptors (MOR) --- p.11 / Chapter 1.2.2 --- Kappa Opioid Receptors (KOR) --- p.14 / Chapter 1.2.3 --- Delta Opioid Receptors (DOR) --- p.15 / Chapter 1.3 --- Dopamine Receptors --- p.17 / Chapter 1.4 --- Dopamine Transporter (DAT) --- p.19 / Chapter 1.5 --- Gamma-Aminobutyric Acid (GABA) Receptors --- p.21 / Chapter 1.6 --- Mesocorticolimbic Pathway --- p.22 / Chapter 1.6.1 --- Neural Substrates of Drug Reinforcement --- p.25 / Chapter 1.6.2 --- Molecular and Cellular Basis of Addiction --- p.26 / Chapter 1.6.3 --- Intracellular Substrates of Relapse --- p.29 / Chapter 1.7 --- Environmental Factors in Drug Addiction --- p.30 / Chapter 1.8 --- Genetic Factors in Drug Addiction --- p.32 / Chapter 1.9 --- Aim of Project --- p.35 / Chapter CHAPTER TWO --- MATERIALS AND METHODS / Chapter 2.1 --- Recruitment of Subjects 、 --- p.39 / Chapter 2.1.1 --- Heroin-dependent Subjects --- p.39 / Chapter 2.1.1.1 --- Phenotype Assessment --- p.39 / Chapter 2.1.1.2 --- Establishment of Socio-demographic Data --- p.40 / Chapter 2.1.2 --- Control Subjects --- p.42 / Chapter 2.2 --- DNA Extraction --- p.42 / Chapter 2.3 --- Genotyping --- p.43 / Chapter 2.3.1 --- A118G Polymorphism in Exon 1 of the Human MOR (hMOR) Gene --- p.43 / Chapter 2.3.2 --- C1031G Polymorphism in Intron 2 of the hMOR Gene --- p.45 / Chapter 2.3.3 --- T921C Polymorphism in Exon 3 of the Human DOR (hDOR) Gene --- p.46 / Chapter 2.3.4 --- 3'VNTR Polymorphism of the DAT Gene --- p.47 / Chapter 2.3.5 --- TaqI A Polymorphism of the DRD2 Gene --- p.48 / Chapter 2.3.6 --- NciI Polymorphism of the GABRG2 Gene --- p.48 / Chapter 2.4 --- DNA Sequencing --- p.49 / Chapter 2.5 --- Statistical Analysis --- p.50 / Chapter CHAPTER THREE --- RESULTS / Chapter 3.1 --- Socio-demographic Data --- p.52 / Chapter 3.1.1 --- Age of the Control and Heroin-dependent Subjects --- p.52 / Chapter 3.1.2 --- Education Standard of the Heroin-dependent Subjects --- p.52 / Chapter 3.1.3 --- Years of Heroin Use --- p.53 / Chapter 3.2 --- Addition Severity Index (ASI) --- p.53 / Chapter 3.2.1 --- ASI-Medical --- p.53 / Chapter 3.2.2 --- ASI-Employment --- p.54 / Chapter 3.2.3 --- ASI-Drug --- p.54 / Chapter 3.2.4 --- ASI-Legal --- p.54 / Chapter 3.2.5 --- ASI-Family/Social Relationships --- p.55 / Chapter 3.2.6 --- ASI-Psychiatry --- p.55 / Chapter 3.2.7 --- Correlation Among the Factors of ASI --- p.55 / Chapter 3.3 --- A118G Polymorphism in Exon 1 of the Human Mu Opioid Receptor (hMOR) Gene --- p.56 / Chapter 3.4 --- C1031G Polymorphism in Intron 2 of the hMOR Gene --- p.58 / Chapter 3.5 --- T921C Polymorphism in Exon 3 of the Human Delta Opioid Receptor (hDOR) Gene --- p.59 / Chapter 3.6 --- Interaction Between Genotypes --- p.60 / Chapter 3.6.1 --- Combined Genotypes of A118G and C1031G Polymorphisms of the hMOR Gene --- p.60 / Chapter 3.6.2 --- Combined Genotypes of A118G Polymorphism of the hMOR Gene and T921C Polymorphism of the hDOR Gene --- p.61 / Chapter 3.6.3 --- Combined Genotypes of C1031G Polymorphism of the hMOR Gene and T921C Polymorphism of the hDOR Gene --- p.61 / Chapter 3.7 --- Correlation Between Allelic Frequencies and Factors of the ASI --- p.62 / Chapter 3.8 --- 3'VNTR Polymorphism of DAT Gene --- p.62 / Chapter 3.9 --- TαqI A Polymorphism of DRD2 Gene --- p.63 / Chapter 3.10 --- NciI Polymorphism of GABRG2 Gene --- p.64 / Chapter CHAPTER FOUR --- DISCUSSION & CONCLUSION --- p.66 / REFERENCES --- p.83 / APPENDIX I The Addiction Severity Index / APPENDIX II Table of Severity Ratings / APPENDIX III Allelic Frequency of A118G Polymorphism in Different Populations / APPENDIX IV Details Information About the Single Nucleotide Polymorphisms In Present Study