초록 ▼

- 코카인을 강박적으로 탐색하는 중독 취약성 마우스와 섭취하지만 강박적인 행동이 없는 저항성 마우스를 성공적으로 분리함.
- Homozygote Drd2-EGFP마우스가 약물 중독에 내재적인 취약성을 가진다는 것을 발견함.
- 중독 취약성을 가지는 마우스에서 일어나는 전기생리학적 변화 및 이온채널 수준에서의 메카니즘을 동정함.
- 중격의지핵의 세포타입 특이적인 MSN-MSN간 억제성 국소회로망은 코카인 장기 노출에 의해 강화되지만 코카인 중독 취약성과는 관련이 없음을 증명함.
- 중격의지핵의 아세틸콜린성 중간뉴

- 코카인을 강박적으로 탐색하는 중독 취약성 마우스와 섭취하지만 강박적인 행동이 없는 저항성 마우스를 성공적으로 분리함.
- Homozygote Drd2-EGFP마우스가 약물 중독에 내재적인 취약성을 가진다는 것을 발견함.
- 중독 취약성을 가지는 마우스에서 일어나는 전기생리학적 변화 및 이온채널 수준에서의 메카니즘을 동정함.
- 중격의지핵의 세포타입 특이적인 MSN-MSN간 억제성 국소회로망은 코카인 장기 노출에 의해 강화되지만 코카인 중독 취약성과는 관련이 없음을 증명함.
- 중격의지핵의 아세틸콜린성 중간뉴런에서 발현되는 D2R의 농도와 그 기능적 여파가 중독 현상과 상관관계가 있음을 보임.

Abstract ▼

Ⅰ. Purpose and necessity of the research project
- Using drug-dependent animal model, the researchers will provide a mechanistic evidence for addiction and craving state, suggesting scientific bases for a novel target for addiction therapy.
- Previously conducted addiction researches did not a

Ⅰ. Purpose and necessity of the research project
- Using drug-dependent animal model, the researchers will provide a mechanistic evidence for addiction and craving state, suggesting scientific bases for a novel target for addiction therapy.
- Previously conducted addiction researches did not address the physiological property in a cell-type specific manner.
- Recently, the advance in optogenetic techniques and systems neuroscience has made researchers to be interested in neural circuit-specific regulation and its consequent behavior.

Ⅱ. Range and contents of the research project
- Advancing self-administration paradigm, drug addiction model using mice was successfully established.
- A transgenic mouse line susceptible to cocaine addiction was identified.
- D1R-MSN specific alteration of cocaine-susceptible mice and drug-addicted mice was observed.
- Local inhibitory circuit in the NAc after exposure to cocaine was addressed in a cell-type specific manner.
- Gene-dose of D2R in NAc cholinergic interneuron has correlation with addiction symptoms.

Ⅲ. Result
- Wild-type mice group was able to be divided in a group compulsively seeking cocaine and a group normally intaking cocaine.
- Homozygote Drd2-EGFP mice exhibits vulnerability to cocaine.
- Mice susceptible to cocaine addiction exhibit a typical alteration in electrophysiological properties.
- Local inhibitory circuit between D2R- and D1R-MSNs were not altered after an acute cocaine injection even in the mice susceptible to cocaine.
- Gene-dose of D2R in NAc cholinergic interneuron has a positive correlation with addiction symptoms.

Ⅳ. Utilization plan of the result
- A follow-up research on relationship between neuronal activity of cholinergic interneuron and the reorganization process of striatal circuit will be conducted.
- The follow-up research project will improve understanding for molecular and systematic mechanism of a susceptibility to drug addiction and will suggest a novel target for treating addiction-related disorder which is known as easy to relapse.