FIGURE 6.

Protein–protein interaction (PPI) network analysis of differentially expressed proteins with and without sub-chronic nicotine. PPI network construction was performed using the STRING database for sex and treatment group comparisons with sufficient numbers of differentially regulated proteins for analysis. Thresholds for analysis were set at an interaction score of >0.7 and FDR of 1%. Further sub-network analysis was performed using the MCODE plug-in in Cytoscape (cut off-values: node score = 0.2, degree = 4, k-core = 4, maximum depth = 100). The top three ranked clusters of networks, or fewer if less than three were identified, are shown. Score, number of nodes, number of edges, and significantly enriched GO and KEGG pathways (p < 0.05) as analyzed using DAVID database are shown for each cluster. (A) Two clusters were identified for MC vs. FC in the VTA of C3H/HeJ mice used for sub-chronic nicotine administration. (B) Only one cluster was identified for FN vs. FC in the VTA after sub-chronic nicotine administration. (C) The top three clusters are shown for MC vs. FC in the NAc shell of C3H/HeJ mice used for sub-chronic nicotine administration. (D) Two clusters were identified for FN vs. FC in the NAc shell after sub-chronic nicotine administration.