Cocaine-Induced Behavioral Sensitization in mice : effects of microinjection of dopamine D2 receptor antagonist into the Nucleus accumbens
- 주제(키워드) addiction , behavioral sensitization , dopamine D2 receptor , Nucleus accumbens
- 발행기관 고려대학교 대학원
- 지도교수 백자현
- 발행년도 2011
- 학위수여년월 2011. 8
- 학위구분 석사
- 학과 일반대학원 생명공학과
- 세부전공 세포생물학 전공
- 원문페이지 44 p
- 실제URI http://www.dcollection.net/handler/korea/000000026966
- 본문언어 영어
- 제출원본 000045669620
초록/요약
Dopamine D2 receptor (D2R) is crucial for addictive behaviors in mesolimbic dopaminergic pathways which receive glutamatergic input from the corticolimbic areas. To determine the role of D2R in cocaine-mediated addictive behaviors, we analyzed the cocaine-induced behavioral sensitization in WT and D2R knockout (D2R-/-) mice. Mice were received D2R antagonist (Raclopride, 2.5nmol or 5nmol) by microinfusion into Nucleus accumbens core (NAcc) following repeated intraperitoneal (i.p.) injection of saline or cocaine (15mg/kg) for 5 days. WT and D2R-/- mice showed a development of cocaine-induced sensitization with increase of locomotor activity and D2R antagonist did not alter cocaine-induced activity in both mice groups. After 14 days of withdrawal, raclopride was infused into NAcc and mice were challenged with lower dose of cocaine (10mg/kg) to test the expression of sensitization. D2R antagonist did not affect the expression of sensitization in both WT and D2R-/- mice. These results suggest that D2R in NAcc is not involved in cocaine-induced behavioral sensitization. We are currently investigating the effect of AMPAR antagonist in these regulations to examine the role of glutamate system in NAcc for cocaine-induced behavioral sensitization.
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List of Tables ………………………………………………ⅰ
List of Figures ………………………………………………ⅱ
Abstract ……………………………………………………ⅲ
Introduction ………………………………………………… 1
Material and Methods …………………………………… 4
1. Mice
2. Drug
3. Surgery
4. Behavior experiment
4-1. Apparatus and locomotor activity
4-2. Experiment Procedure
5. Assessment of cannula placement
6. Surface protein biotinylation
7. Western blotting
Results …………………………………………………….. 9
1. Effect of D2R antagonist (Raclopride 2.5nmol or 5nmol) in development of cocaine-induced behavioral sensitization.
2. Effect of D2R antagonist (Raclopride 2.5nmol or 5nmol) in expression of cocaine-induced behavioral sensitization.
3. Surface expression of AMPA receptor.
4. Effect of AMPA receptor antagonist (CNQX 1nmol) of cocaine-induced behavioral sensitization.
Discussion …………………………………………………. 30
References …………………………………………………. 32
Abstract in Korean ………………………………………. 37
