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

Wan Lei Nei. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (leaves 126-160). / Abstract and questionnaires in English and Chinese. / Acknowledgement --- p.vi / Abstract --- p.vii / List of abbreviations --- p.xii / Chapter CHAPTER ONE --- INTRODUCTION --- p.1 / Chapter 1.1 --- Club drugs --- p.1 / Chapter 1.1.1. --- "Pattern of ""club drug"" use in Hong Kong" --- p.2 / Chapter 1.1.2. --- "Popular ""club drugs"" used in Hong Kong and their effects" --- p.4 / Chapter 1.1.2.1. --- MDMA ('ecstasy') --- p.4 / Chapter 1.1.2.2. --- Ketamine --- p.7 / Chapter 1.1.2.3. --- Cannabis --- p.10 / Chapter 1.1.2.4. --- Methamphetamine ´(بIce'） --- p.12 / Chapter 1.2 --- Neurobiology of drug addiction --- p.13 / Chapter 1.2.1 --- Introduction to reward pathways and animal models of addiction --- p.13 / Chapter 1.2.2 --- Mesocorticolimbic dopamine pathway --- p.15 / Chapter 1.2.3 --- Behavioural processes of addiction --- p.18 / Chapter 1.2.4 --- Other neurotransmitter systems in addiction --- p.21 / Chapter 1.2.5 --- Molecular plasticity in addiction: signaling and gene expression --- p.23 / Chapter 1.3 --- Association of Personality Traits and Drug Abuse --- p.26 / Chapter 1.4. --- Association between genetics and drug abuse --- p.31 / Chapter 1.4.1 --- "Family, twin and adoption studies" --- p.32 / Chapter 1.4.2 --- Transgenic and knock out animal models --- p.33 / Chapter 1.4.3 --- Candidate genes for drug abuse --- p.33 / Chapter 1.4.3.1 --- Dopamine receptor genes --- p.34 / Chapter 1.4.3.2 --- Monoamine Oxidase (MAO) gene --- p.35 / Chapter 1.4.3.3 --- Catechol-O-methyltransferase (COMT) gene --- p.35 / Chapter 1.4.3.4 --- Serotonergic genes --- p.37 / Chapter 1.4.3.5 --- Opioid receptor genes --- p.38 / Chapter 1.4.4 --- Linkage studies of drug abuse --- p.39 / Chapter 1.5 --- Genetic factor and personality trait --- p.39 / Chapter 1.5.1 --- Twins study --- p.41 / Chapter 1.5.2 --- Candidate gene studies --- p.41 / Chapter 1.5.3.1 --- Dopamine (DA) --- p.42 / Chapter 1.5.3.2 --- COMT --- p.43 / Chapter 1.5.3.3 --- MAO-A --- p.44 / Chapter 1.5.3.4 --- Serotonin (5-HT) --- p.44 / Chapter 1.5.3.5 --- Opioid receptor --- p.46 / Chapter 1.5.4 --- Interaction between genes --- p.47 / Chapter 1.6 --- Aim of study --- p.47 / Chapter CHAPTER TWO --- MATERIALS AND METHODS --- p.50 / Chapter 2.1 --- Recruitment of Subjects --- p.50 / Chapter 2.1.1. --- Club drug users --- p.50 / Chapter 2.1.2. --- Controls --- p.50 / Chapter 2.2 --- Phenotype assessment --- p.51 / Chapter 2.2.1 --- Questionnaire (Appendix la 226}0ؤ Chinese version used; lb - English translated version for reference only) --- p.51 / Chapter 2.2.1.1 --- Demographics --- p.51 / Chapter 2.2.1.2 --- Pattern of drug use --- p.52 / Chapter 2.2.1.3 --- First time drug use --- p.52 / Chapter 2.2.1.4 --- Reason of drug use --- p.52 / Chapter 2.2.1.5 --- Effects of drug use --- p.52 / Chapter 2.2.1.6 --- Potential dependence/ withdrawal --- p.53 / Chapter 2.2.1.7 --- Knowledge about drug of abuse and psychological well-being. --- p.53 / Chapter 2.2.2 --- Personality assessments (Appendix 2a - Chinese version of SSS-V scale; 2b -Chinese version of BIS/BAS scale) --- p.53 / Chapter 2.3 --- DNA extraction --- p.53 / Chapter 2.4 --- Genotyping --- p.54 / Chapter 2.4.1 --- "G1947A, Val108/158 Met polymorphism in the catechol-O-methyltransferase (COMT) gene" --- p.55 / Chapter 2.4.2 --- T941G polymorphism in the monoamine oxidase A (MAO-A) gene --- p.55 / Chapter 2.4.3 --- TaqI A Polymorphism of the DRD2 Gene --- p.56 / Chapter 2.4.4 --- 7-repeat allele of a 48 bp repeat polymorphism (DRD4-7) in exon 3 of the dopamine D4 receptor gene (DRD4) --- p.57 / Chapter 2.4.5 --- -521C/T single nucleotide polymorphism (SNP) I the promoter region of the dopamine D4 receptor gene (DRD4) --- p.58 / Chapter 2.4.6 --- G861C polymorphism in the serotonin receptor 1B (5-HT1B) gene --- p.59 / Chapter 2.4.7 --- The 44 bp insertion/deletion polymorphism in the promoter region of the serotonin transporter gene (SLC6A4) --- p.60 / Chapter 2.4.8 --- T921C Polymorphism in Exon 3 of the Human DOR (hDOR) Gene --- p.60 / Chapter 2.4.9 --- A118G polymorphism in Exon 1 of the Human MOR (hMOR) Gene --- p.61 / Chapter 2.5 --- DNA sequencing --- p.62 / Chapter 2.6 --- Statistical Analysis --- p.63 / Chapter CHAPTER THREE --- RESULTS --- p.65 / Chapter 3.1 --- Results from questionnaire --- p.65 / Chapter 3.1.1 --- Demographics of club drug users --- p.65 / Chapter 3.1.1.1 --- Gender and age --- p.65 / Chapter 3.1.1.2 --- District of residence --- p.65 / Chapter 3.1.1.3 --- Type of living quarters and cohabitation --- p.65 / Chapter 3.1.1.4 --- Educational attainment and employment status --- p.66 / Chapter 3.1.1.5 --- Parents'details --- p.66 / Chapter 3.1.2 --- First time drug use --- p.67 / Chapter 3.1.3 --- Prevalence of drug use --- p.68 / Chapter 3.1.4 --- Frequency and quantity of drug used --- p.69 / Chapter 3.1.7 --- Drug spending --- p.70 / Chapter 3.1.8 --- Pattern of drug use in and outside Hong Kong --- p.71 / Chapter 3.1.9 --- Cause of drug use --- p.75 / Chapter 3.1.10 --- The negative effects of drug use --- p.77 / Chapter 3.1.11. --- Potential tolerance/ dependence --- p.79 / Chapter 3.1.12 --- Knowledge about drugs of abuse --- p.80 / Chapter 3.1.13 --- Psychological well-being --- p.80 / Chapter 3.2 --- Personality trait assessments --- p.81 / Chapter 3.2.1 --- Personality traits between club drugs users and controls --- p.81 / Chapter 3.2.2 --- Personality trait by gender --- p.81 / Chapter 3.2.3 --- Reliability --- p.83 / Chapter 3.3 --- Genotyping --- p.84 / Chapter 3.3.1 --- "G1947A,Vall08/158 Met polymorphism in the catechol-O-methyl- transferase (COMT) gene" --- p.84 / Chapter 3.3.2 --- T941G polymorphism in the monoamine oxidase A (MAO-A) --- p.87 / Chapter 3.3.3 --- T921C Polymorphism in Exon 3 of the Human DOR (hDOR) Gene --- p.90 / Chapter 3.3.4 --- G861C polymorphism in the serotonin receptor 1B (5-HT1B) gene --- p.92 / Chapter 3.3.5 --- TaqI A Polymorphism of the DRD2 Gene --- p.94 / Chapter 3.3.6 --- The All 8G polymorphism in exon 1 of the human MOR (hMOR) gene --- p.96 / Chapter 3.3.7 --- The 44 bp insertion/deletion polymorphism in the promoter region of the serotonin transporter gene (SLC6A4) --- p.97 / Chapter 3.3.8 --- 48bp repeat polymorphism (DRD4) in exon 3 of the dopamine D4 receptor gene (DRD4) --- p.98 / Chapter 3.3.9 --- -521C/T polymorphism in the promoter region of the dopamine D4 receptor gene (DRD4) --- p.99 / Chapter CHAPTER FOUR --- DISCUSSION --- p.100 / Chapter 4.1 --- Demographics and pattern of club drug use --- p.100 / Chapter 4.2 --- Personality traits assessment --- p.108 / Chapter 4.3 --- Gene polymorphisms --- p.110 / Chapter 4.3.1 --- "COMT G1947A, Val108/158 Met polymorphism" --- p.111 / Chapter 4.3.2. --- MAO-A T941G polymorphism --- p.114 / Chapter 4.3.3. --- hDOR T921C polymorphism --- p.115 / Chapter 4.3.4. --- hMOR A118G polymorphism --- p.117 / Chapter 4.3.5 --- DRD2 TaqI A polymorphism --- p.118 / Chapter 4.3.6 --- DRD4 48bp VNTR polymorphism --- p.120 / Chapter 4.3.7. --- DRD4 -C521T polymorphism --- p.121 / Chapter 4.3.8. --- 5-HT1B G861C polymorphism --- p.121 / Chapter 4.3.9. --- 5-HTTLPR SLC6A4 44 bp insertion/deletion polymorphism --- p.122 / REFERENCES --- p.125 / APPENDIX 1a Questionnaire (Chinese version) / APPENDIX 1b Questionnaire (English translated version) / APPENDIX 2a Chinese version of SSS-V scale / APPENDIX 2b Chinese version of BIS/BAS scale