针对对吗啡敏感多巴胺基神经元的线粒体动力学改善了阿片类药物戒断
Changyou Jiang1,2, Han Huang1,2, Xiao Yang1,2
1State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science and School of Basic Medical Sciences, Departments of Neurosurgery and Hand Surgery, Huashan Hospital, Fudan University, Shanghai, China.
The Journal of clinical investigation
|January 18, 2024
概括
慢性阿片类药物使用会损害多巴胺神经元,导致戒断. 在这些多巴胺组合中恢复线粒体功能 (Mfn1) 通过减少氧化应激来缓解阿片类药物戒断症状.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 长期使用阿片类药物会导致多巴氨基神经元功能障碍.
- 对阿片类药物戒断的治疗目标,特别是在阿片类药物反应性多巴胺基组合中,需要进一步调查.
研究的目的:
- 为了研究在阿片类药物戒断过程中,腹膜区域 (VTA) 的多巴胺基组合的作用.
- 探索线粒体功能障碍作为阿片类药物使用障碍的治疗标.
主要方法:
- 使用一种依赖神经元活动的Tet-Off系统来标记暴露于吗啡的多巴胺基组合 (Mor-Ens).
- 采用光纤光度和转录组分析来评估神经元活动和分子变化.
- 研究了Mfn1恢复和线粒体分裂抑制 (Mdivi-1) 对阿片类药物戒断的影响.
主要成果:
- 慢性吗啡降低了自发活动的调节,并在VTA多巴胺作用的Mor-Ens.中失调了线粒体呼吸和通路.
- 阿片类药物戒断与线粒体碎片化和线粒素1 (Mfn1) 表达率下降有关.
- 恢复Mfn1或通过Mdivi-1减弱氧化应激和阿片类药物戒断症状抑制线粒体分裂,而不会影响吗啡止痛.
结论:
- 线粒体结构,特别是Mfn1介导的融合,在慢性阿片类药物暴露期间,在多巴胺类神经元的不适应性可塑性中发挥着关键作用.
- 准线粒体动力学是缓解阿片类药物戒断和阿片类药物使用障碍的有希望的治疗策略.
相关概念视频
Opioid Analgesics: Synthetic and Semisynthetic Opioids
300
Synthetic and semisynthetic opioids are pivotal in pain management and tackling opioid addiction. Semisynthetic opioids, including morphinans (morphine derivatives), oxycodone, oxymorphone, hydrocodone, and hydromorphone, have improved pharmacokinetic profiles compared to morphine. Additionally, heroin and 6-MAM (6-Monoacetylmorphine) show better CNS penetration than morphine due to heightened lipid solubility. Hydromorphone, a potent opioid, undergoes hepatic metabolism to form the active...
300
Analgesia and Pain Management
625
Pain is critical to various clinical pathologies, provoking an urgent need for effective management. Pain, whether acute or chronic, is a complex neurochemical process. Its alleviation depends on the type, with nonopioid analgesics effective for mild to moderate pain, such as musculoskeletal or inflammatory pain, while neuropathic pain responds best to anticonvulsants, tricyclic antidepressants, or serotonin/norepinephrine reuptake inhibitors. For severe acute or chronic pain, opioids may be...
625
Opioid Receptors: Overview
847
Opioid receptors, including the mu (μ, MOR), delta (δ, DOR), and kappa (κ, KOR) types, belong to the rhodopsin family of G protein-coupled receptors. These receptors are located throughout the central and peripheral nervous systems and in non-neuronal tissues such as macrophages and astrocytes. Opioid receptor ligands can be categorized into agonists or antagonists. Highly selective agonists include [d-Ala2, MePhe4, Gly(ol)5]-enkephalin or DAMGO for MOR, [D-Pen2,...
847
Opioid Analgesics: Morphine and Other Natural Cogeners
251
Opioids are a class of drugs that mimic endogenous opioid peptides and act on opioid receptors, and help in pain relief. These compounds are classified as natural, synthetic, or semi-synthetic. Natural opioids, like morphine, codeine, and thebaine, are derived from the opium poppy plant (Papaver somniferum or Papaver album) and are termed opiates. Synthetic opioids are artificial, while semi-synthetic opioids combine natural and synthetic compounds. Morphine, a prototypical opioid, possesses a...
251
Drug Abuse and Addiction: Pharmacological Phenomena
476
Drug dependence, abuse, and addiction are complex phenomena that can precipitate various abnormal states. Physical dependence refers to a state of pharmacological adaptation to a drug. This adaptation often results in tolerance—a reduced response to the drug after repeated administrations. When the drug use is abruptly stopped, withdrawal symptoms occur due to the body's need to readjust from the pharmacologically induced imbalance. However, tolerance and withdrawal symptoms do not...
476
Drugs Affecting Neurotransmitter Synthesis
1.4K
Drugs affecting neurotransmitter synthesis can impact the adrenergic neuron and the synthesis of neurotransmitters. For example, α-methyltyrosine and carbidopa target specific enzymes involved in catecholamine synthesis. α-methyltyrosine inhibits the enzyme tyrosine hydroxylase, which converts tyrosine into dopamine. By blocking this enzyme, α-methyltyrosine reduces dopamine production and other catecholamines. Carbidopa, on the other hand, inhibits the enzyme dopa decarboxylase,...
1.4K


