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In this study, we employed transcriptome sequencing, untargeted metabolomics and integrative multi\u2010omics analysis to elucidate the molecular mechanisms underlying nicotine withdrawal\u2010induced affective symptoms, specifically anxiety and depression\u2010like behaviours, within the cerebellum. Our findings demonstrate that enhanced purine metabolism and disrupted arginine metabolism in the cerebellum significantly contribute to the development of anxiety and depression\u2010like behaviours in mice undergoing nicotine withdrawal. Treatment with the non\u2010selective adenosine receptor antagonist, theobromine, markedly alleviates these behaviours. 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