Pathway analysis revealed that pathways related to neurodevelopment were enriched in NAGenes, which further verified the existence of close relationship between the pathology of nicotine addiction and the signaling pathways of nervous system. Four pathways that were related to monoamine neurotransmitters were found to be enriched in the NAGenes, consistent with their central roles in the development of nicotine addiction. Stimulation of nicotinic acetylcholine receptors (nAChR) releases a variety of neurotransmitters in the brain, e.g., dopamine, serotonin, glutamate and GABA. Dopamine is critical for the reinforcing effects or rewarding behaviors of nicotine [37–38], glutamate and GABA are respectively major excitatory and inhibitory neurotransmitter and both of them play important roles in the development of nicotine addiction [39–40]. These neurotransmitters interact with the specific receptors, triggering a series of neuronal signaling pathways and then ultimately realize the regulation of various physiological processes. Of note, our analysis indicated that two pathways, synaptic long term potentiation and synaptic long term depression, were also enriched in genes associated with nicotine addiction. Repeated stimulation of nicotine to nervous system ultimately can modify the neural circuitry
