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<p>Methamphetamine (METH) addiction causes serious psychiatric and neurological disorders, while the overall efficacy of current interventions remains unsatisfactory. Endurance exercise is one effective approach to facilitate drug abstinence and functional rehabilitation, although its exact mechanism has not been fully elucidated. In the current work, we successfully suppressed drug craving behaviors in METH addicts by 48 weeks of aerobic exercise, and a metabolomics study indicated the elevation of serum N−Acetylneuraminic acid (Neu5Ac) specifically in exercised individuals. Further studies in rodent models of METH exposure replicated both behavioral improvement and the increase of Neu5Ac levels in circulation and the striatum. More importantly, we demonstrated that exercise stimulated the hepatic tissues to synthesize Neu5Ac, which modulates synaptic protein in the striatum to alleviate METH-seeking behaviors. In sum, our results propose a liver-brain axis in which exercise reshapes liver metabolism to facilitate drug abstinence.</p>

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Endurance exercise relieves methamphetamine craving behaviors via hepatic synthesis of N−Acetylneuraminic acid

  • 期刊论文

  • 发表日期：

    2026年5月30日

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  • Xue Li,
  • Jisheng Xu,
  • Changling Wei,
  • Xuejie Zhang,
  • Yuanting Zhang,
  • Yu Jin,
  • Xulin Zhou,
  • Yan Yang,
  • Guosi Ying,
  • Li Zhang

摘要

Methamphetamine (METH) addiction causes serious psychiatric and neurological disorders, while the overall efficacy of current interventions remains unsatisfactory. Endurance exercise is one effective approach to facilitate drug abstinence and functional rehabilitation, although its exact mechanism has not been fully elucidated. In the current work, we successfully suppressed drug craving behaviors in METH addicts by 48 weeks of aerobic exercise, and a metabolomics study indicated the elevation of serum N−Acetylneuraminic acid (Neu5Ac) specifically in exercised individuals. Further studies in rodent models of METH exposure replicated both behavioral improvement and the increase of Neu5Ac levels in circulation and the striatum. More importantly, we demonstrated that exercise stimulated the hepatic tissues to synthesize Neu5Ac, which modulates synaptic protein in the striatum to alleviate METH-seeking behaviors. In sum, our results propose a liver-brain axis in which exercise reshapes liver metabolism to facilitate drug abstinence.