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It is vital for protein balance, neurotransmitter release, synaptic function, and neuron survival. The role of macroautophagy in substance use disorders is dual. On one hand, substances like cocaine, methamphetamine, opiates, and alcohol can activate macroautophagy pathways to degrade various neuroinflammatory factors in neuronal cells, providing a protective function. On the other hand, long\u2010term and excessive use of addictive substances can inhibit macroautophagy pathways, obstructing the fusion of autophagosomes with lysosomes and losing the original protective function. This review first summarizes the key proteins and signaling pathways involved in macroautophagy, including mTORC1, AMPK, and endoplasmic reticulum stress, and suggests that the regulation of macroautophagy plays a central role in drug\u2010rewarding behavior and addiction. 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