Title Page
Contents
LIST OF ABBREVIATIONS 14
Abstract 18
Introduction 20
Cigarette Smoking 20
Nicotine Addiction 22
Mechanism of Nicotine 24
Nicotine Withdrawal symptoms 29
Nicotine Addiction Treatments 29
Bupropion 31
Varenicline 32
Nicotine Replacement Therapy 36
Chapter 1. [제목없음] 37
Acanthopanax Koreanum Nakai 37
Acanthopanax Koreanum Nakai Extract 38
Aim of the chapter 40
Materials and Methods 41
Animals 41
Drugs 41
AK extract preparation 43
High-performance liquid chromatography (HPLC) Analysis 43
Behavioral tests 45
Conditioned place preference test 45
Locomotor sensitization 47
Self-administration test 49
Withdrawal symptoms observation 51
Molecular test 51
Evaluation of blood cotinine levels 51
Dopamine Elisa 52
Tissue collection, RNA preparation, and qRT-PCR 53
Protein extraction and western blot analysis 56
Data and statistical analyses 58
Result 59
AK extract on CPP score and locomotor sensitization 59
AK extract on self-administration test 61
AK extract on withdrawal behavioral responses 63
Cotinine and dopamine concentration in the NAcc 65
Dopamine-related gene expression of AK extract 67
The expression level of nAChR in the VTA by acute nicotine treatment 69
The expression level of nAChR in the VTA by repeated nicotine treatment 71
Effect of AK extract in the DRD1-EPAC2-ERK-CREB pathway 73
PART 1. SUMMARY 75
Chapter 2. [제목없음] 76
INTRODUCTION 76
Eleutheroside B 76
Chlorogenic Acid 78
Aim of the study 80
Result 81
HPLC Analysis 81
EB and CGA on CPP and locomotor sensitization 82
EB and CGA on self-administration test 84
EB and CGA on withdrawal responses 86
Effect of EB and CGA on dopamine concentration in the NAcc 88
The expression level of nAChR in the VTA by acute nicotine treatment 89
The expression level of nAChR in the VTA by repeated nicotine treatment 91
Effect of EB and CGA in the DRD1-EPAC2-ERK-CREB pathway 93
PART 2. SUMMARY 95
Discussion 96
CONCLUSION 104
References 106
국문초록 124
Table 1. Sequences of PCR primer for qRT-PCR 55
Table 2. Primary antibody information 57
Fig 1. Effects of Smoking 21
Fig 2. Development of nicotine addiction 23
Fig 3. Mechanism of nicotine addiction 28
Fig 4. Mechanism of Varenicline 35
Fig 5. Drugs structure 42
Fig 6. HPLC analysis diagram 44
Fig 7. The CPP test diagram 46
Fig 8. The locomotor sensitization test 48
Fig 9. The self-administration test 50
Fig 10. Workflow of qRT-PCR 55
Fig 11. The effects of AK extract on CPP and locomotor sensitization. 60
Fig 12. The effects of AK extract on the nicotine self-administration test. 62
Fig 13. The effects of AK extract on withdrawal symptoms. 64
Fig 14. The concentration of cotinine and dopamine in NAcc. 66
Fig 15. mRNA levels of the dopamine-related system. 68
Fig 16. The effects of acute treatment of AK extract on the expression of nAChR α4, α7, and β2 in VTA. 70
Fig 17. The effects of AK extract repeated treatment on the expression of nAChR α4, α7, and β2 in VTA. 71
Fig 18. The effects of AK extract repeated treatment on the expression of DRD1, Epac 2, ERK, and CREB in NAcc. 74
Fig 19. Chromatogram of Acanthopanax koreanum extract using HPLC analysis. 81
Fig 20. The effects of EB, CGA on CPP and locomotor sensitization. 83
Fig 21. The effects of EB, and CGA on the nicotine self-administration test. 85
Fig 22. The effects of EB, and CGA on withdrawal symptoms. 87
Fig 23. The effects of EB, CGA on dopamine concentration in NAcc. 88
Fig 24. The effects of acute treatment of EB, and CGA on the expression of nAChR α4, α7, and β2 in VTA. 90
Fig 25. The effects of repeated treatment of EB, and CGA on the expression of nAChR α4, α7, and β2 in VTA. 92
Fig 26. The effects of EB, CGA on the expression of DRD1, Epac 2, ERK, and CREB in NAcc. 94
Fig 27. Diagram illustrating the effects of AK extract and components (EB, CGA) on the nAChR α4, α7, β2 (VTA), and DRD1-EPAC-ERK-CREB pathway. 105