were critical in synaptic plasticity development and have been reported to be involved in addiction [26–27]. In addition, we also highlighted other significantly enriched pathways, i.e., cAMP-mediated signaling, calcium signaling, G-protein coupled receptor signaling, neuropathic pain signaling in dorsal horn neurons and CREB signaling in neurons. This result was consistent with prior knowledge of nicotine addiction [28–30], providing valuable evidence for the study of molecular mechanism underlying nicotine addiction. Of note, we found many pathways that were related to immune system in the list, in line with previous reports that nicotine might have effects on organism’s immune [2, 31]. Moreover, three pathways related to retinoid X receptor (RXR) were found to be enriched in the NAGenes, i.e., LPS/IL-1 mediated inhibition of RXR function, PXR (pregnane X receptor)/RXR activation and LXR (liver X receptor)/RXR activation. RXR, a kind of nuclear receptor, is a master regulator during ligand-induced transcription activities [32]. In summary, these results suggest that neurodevelopment, immune and metabolic systems play important roles in the pathogenesis of nicotine addiction.
