The development of gene therapy with neuroimmune protein against drug addiction

• Project/Area Number: 25860392
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Applied pharmacology
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: MURAKAMI Gen 浜松医科大学, 医学部, 特任研究員 (70613727)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 主要組織適合遺伝子複合体 / 薬物依存 / コカイン / 自己投与 / ドーパミン / 腹側被蓋野

Outline of Final Research Achievements

MHC class I (MHCI), an important immune protein, contributes to eliminate synaptic connections in various brain regions, and its deficiency results in brain dysfunctions. However, the contribution of MHCI to addictive behaviors has not been considered. Here we found that repeated cocaine intakes persistently reduce MHCI expression particularly in dopamine neurons that is important for brain reward functions. This reduction leads to enduring potentiation of synaptic inputs to these neurons, resulting in robust cocaine-seeking behavior that is an animal model of relapse to cocaine. By contrast, cocaine-seeking behavior was suppressed by restoring the cocaine-induced reduction of MHCI in dopamine neurons. These results suggest that MHCI regulates synaptic transmission in dopamine neurons and its reduction underlies animal model of relapse to cocaine.

Research Products

• [Journal Article] Functional deficiency of MHC class I enhances LTP and abolishes LTD in the nucleus accumbens of mice. (2014)
  • Author(s): Edamura, M., Murakami, G., Meng, H., Itakura, M., Shigemoto R., Fukuda, A. and Nakahara, D.
  • Journal Title: PLoS ONE Volume: 9 Issue: 9 Pages: e107099-e107099
  • DOI: 10.1371/journal.pone.0107099
  • Peer Reviewed / Open Access
• [Presentation] Involvement of Immune Protein MHC class I in The Development of Cocaine Self-Administration (2014)
  • Author(s): Murakami Gen
  • Organizer: Society for neuroscience
  • Place of Presentation: Washington D.C.
  • Year and Date: 2014-11-15
• [Presentation] Involvement of Immune Protein MHC class I in Cocaine-seeking Behavior (2014)
  • Author(s): 村上元
  • Organizer: 第19会静岡健康・長寿学術フォーラム
  • Place of Presentation: 静岡県
  • Year and Date: 2014-11-07
• [Presentation] 免疫分子であるMHCクラス1がドーパミン神経細胞を修飾しマウスのコカイン探索行動を維持する (2014)
  • Author(s): 村上元
  • Organizer: 第14回浜松医科学シンポジウム
  • Place of Presentation: 静岡県
  • Year and Date: 2014-11-06
  • Invited
• [Presentation] Involvement of Immune Protein MHC class I in The Development of Cocaine Self-Administration (2014)
  • Author(s): 村上元
  • Organizer: 第37回日本神経科学会
  • Place of Presentation: 神奈川県
  • Year and Date: 2014-09-12
• [Presentation] Cellular Mechanisms of Enhanced Cocaine Self-Administration in MHC Class Ι Deficient Mice (2013)
  • Author(s): Murakami Gen
  • Organizer: Society for Neuroscience
  • Place of Presentation: San Diego, USA
• [Remarks] 浜松医科大学心理学
  • URL: http://www.hama-med.ac.jp/uni_education_igakubu_igaku_shinri.html