Department of Forensic Science, School of Basic Medical Science, Central South University, Changsha, Hunan 410013, China; Clinical Medicine Eight-Year Program, Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, China.
Department of Forensic Science, School of Basic Medical Science, Central South University, Changsha, Hunan 410013, China.
Biomed Pharmacother. 2024 Apr;173:116414. doi: 10.1016/j.biopha.2024.116414. Epub 2024 Mar 9.
Drug-associated long-term memories underlie substance use disorders, including heroin use disorder (HUD), which are difficult to eliminate through existing therapies. Addictive memories may become unstable when reexposed to drug-related cues and need to be stabilized again through protein resynthesis. Studies have shown the involvement of histone acetylation in the formation and reconsolidation of long-term drug-associated memory. However, it remains unknown whether and how histone acetyltransferases (HAT), the essential regulators of histone acetylation, contribute to the reconsolidation of heroin-associated memories. Herein, we investigated the function of HAT in the reconsolidation concerning heroin-conditioned memory by using a rat self-administration model. Systemic administration of the HAT inhibitor garcinol inhibited cue and heroin-priming induced reinstatement of heroin seeking, indicating the treatment potential of garcinol for relapse prevention.
药物相关的长期记忆是物质使用障碍的基础，包括海洛因使用障碍（HUD），这是现有治疗方法难以消除的。当重新接触到与药物相关的线索时，成瘾记忆可能会变得不稳定，需要通过蛋白质重新合成来再次稳定。研究表明，组蛋白乙酰化参与了长期药物相关记忆的形成和再巩固。然而，目前尚不清楚组蛋白乙酰转移酶（HAT）是否以及如何参与海洛因相关记忆的再巩固，HAT 是组蛋白乙酰化的必要调节因子。在此，我们通过大鼠自身给药模型研究了 HAT 在海洛因条件记忆再巩固中的作用。系统给予 HAT 抑制剂 garcinol 可抑制线索和海洛因引发的觅药行为复燃，表明 garcinol 具有预防复发的治疗潜力。
