As a major eukaryotic cell clearing machinery, autophagy grants cell proteostasis, which is key for neurotransmitter release, synaptic plasticity, and neuronal survival. In line with this, besides neuropathological events, autophagy dysfunctions are bound to synaptic alterations that occur in mental disorders, and early on, in neurodegenerative diseases. This is also the case of methamphetamine (METH) abuse, which leads to psychiatric disturbances and neurotoxicity. While consistently altering the autophagy machinery, METH produces behavioral and neurotoxic effects through molecular and biochemical events that can be recapitulated by autophagy blockade. These consist of altered physiological dopamine (DA) release, abnormal stimulation of DA and glutamate receptors, as well as oxidative, excitotoxic, and neuroinflammatory events. Recent molecular insights suggest that METH early impairs the autophagy machinery, though its functional significance remains to be investigated. Here we discuss evidence suggesting that alterations of DA transmission and autophagy are intermingled within a chain of events underlying behavioral alterations and neurodegenerative phenomena produced by METH. Understanding how METH alters the autophagy machinery is expected to provide novel insights into the neurobiology of METH addiction sharing some features with psychiatric disorders and parkinsonism.

作为一种主要的真核细胞清除机制，自噬赋予细胞蛋白质稳态，这是神经递质释放、突触可塑性和神经元存活的关键。与此一致，除了神经病理学事件外，自噬功能障碍与精神障碍和早期神经退行性疾病中发生的突触改变有关。这也是甲基苯丙胺 (METH) 滥用的情况，这会导致精神障碍和神经毒性。在不断改变自噬机制的同时，METH 通过分子和生化事件产生行为和神经毒性效应，这些效应可以通过自噬阻断来概括。这些包括改变的生理多巴胺 (DA) 释放、DA 和谷氨酸受体的异常刺激，以及氧化、兴奋性毒性和神经炎症事件。最近的分子见解表明，METH 早期会损害自噬机制，尽管其功能意义仍有待研究。在这里，我们讨论的证据表明 DA 传递和自噬的改变混合在由 METH 产生的行为改变和神经退行性现象的一系列事件中。了解 METH 如何改变自噬机制有望为 METH 成瘾的神经生物学提供新的见解，这些神经生物学与精神疾病和帕金森症具有一些共同特征。在这里，我们讨论的证据表明 DA 传递和自噬的改变混合在由 METH 产生的行为改变和神经退行性现象的一系列事件中。了解 METH 如何改变自噬机制有望为 METH 成瘾的神经生物学提供新的见解，这些神经生物学与精神疾病和帕金森症具有一些共同特征。在这里，我们讨论的证据表明 DA 传递和自噬的改变混合在由 METH 产生的行为改变和神经退行性现象的一系列事件中。了解 METH 如何改变自噬机制有望为 METH 成瘾的神经生物学提供新的见解，这些神经生物学与精神疾病和帕金森症具有一些共同特征。