Role of Accumbal Medium Spiny Neurons Expressing Dopamine D2 Receptors on Cocaine-Induced Behavioral Sensitization
- 주제(키워드) dopamine , nucleus accumbens , Dopamine D2 receptor , addiction , optogenetics
- 발행기관 고려대학교 대학원
- 지도교수 백자현
- 발행년도 2016
- 학위수여년월 2016. 2
- 학위구분 석사
- 학과 대학원 생명과학과
- 원문페이지 44 p
- 실제URI http://www.dcollection.net/handler/korea/000000066293
- 본문언어 영어
- 제출원본 000045867178
초록/요약
Addictive behaviors resulting from chronic cocaine exposure have been proposed to involve synaptic modifications within the nucleus accumbens. Optogenetics was used to further investigate the role of medium spiny neurons (MSNs) expressing dopamine D2 receptors (D2R) in the nucleus accumbens (NAc) on cocaine-induced behavioral sensitization. Archaerhodopsin (ArchT), a neuronal silencer, was coded in adeno-associated viral vectors and delivered to the nucleus accumbens of D2 Cre transgenic mice. Using the cre/loxp systems I was able to selectively inhibit D2R-expressing medium spiny neurons in the nucleus accumbens. Photoinhibition of D2R-MSNs in the NAc did not affect basal locomotor activity unlike photoactivation of D2R-MSNs, which caused attenuation of locomotor activity. In addition, photoinhibition of accumbal D2R-MSNs during the initiation of sensitization did not affect the expression of cocaine-induced behavioral sensitization. When photoinhibition of D2R-MSNs in the NAc was administered consecutively during the withdrawal period from cocaine, no affect was observed on the expression of cocaine-induced behavioral sensitization. Photoinhibition of D2R-MSNs in the NAc during the initiation and withdrawal period did not affect the expression of cocaine-induced sensitization suggesting that silencing NAc D2R-MSNs do not directly modulate drug addictive behaviors. Additional molecular mechanisms must be studied in order to further elucidate the role of accumbal D2R-MSNs on cocaine-induced addictive behaviors.
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CONTENTS
List of Figures ……………………………………………… 1
Abstract …………………………………………………… 2
Introduction ………………………………………………… 3
Material and Methods …………………………………… 7
1. Mice
2. Viral packaging and delivery
3. Surgical Procedures and optic cannula implantation
4. In vivo optic stimulation
5. Behavioral analysis
6. Cocaine sensitization
7. Immunofluorescence
8. Cholera toxin B injection
9. Statistical analysis
Results ……………………………………………………… 12
1. Effect of photostimulation of NAc D2R-MSNs on the expression of cocaine-induced sensitization
2. Effect of photoinhibition of NAc D2R-MSNs on the expression of cocaine-induced sensitization
3. Retrogradal tracing using cholera toxin b to determine inputs into the nucleus accumbens core
Discussion …………………………………………………. 30
References …………………………………………………. 34
Acknowledgements ……………………………………….. 38
