Of significance, in pathway crosstalk analysis we identified three main modules. One module was mainly dominated by the pathways associated with the activity of the nervous system. Among these pathways, dopamine-DARPP32 feedback in cAMP signaling, glutamate receptor signaling, neuropathic pain signaling in dorsal horn neurons, and CREB signaling in neurons have been well studied to be involved in neuron or central nervous system (CNS) [49–51]. For instance, CREBs, widely been accepted as prototypical transcription factors, play a critical role in biological processes such as neuronal plasticity, learning and memory. Meanwhile, several lines of evidence have pointed that alterations of the activity of CREB by drugs of abuse have a profound effect on behavioral manifestations of drug reward and withdrawal [52]. Subsequently, we collected the genes contributing to the crosstalk, and the most frequently shared genes included glutamate receptor ionotropic N-methyl D-aspartate 2A (GRIN2A), GRIN2B, GRIN3A, calcium/calmodulin-dependent protein kinase IV (CAMK4), CREB1, and glutamate receptor metabotropic 7 (GRM7), suggesting these genes might be more potential targets in the development of nicotine addiction. In addition, the pathway pair of cAMP-mediated signaling and
