(p≤0.001), RASGRP2 (RAS guanyl releasing protein 2), encodes a brain-enriched nucleotide that contains an N-terminal GEF domain and may also play a role in cell signaling. The emerging functional themes related to the top genes in our data appear to be cellular processing and actin cytoskeleton restructuring; these are also identified in molecular studies investigating alcohol and cocaine addiction [55] and are therefore consistent with molecular models of addiction. It is already known that chronic and dependent drug consumption is correlated with structural plasticity in relevant neural circuits [56] and that such experience-dependent plasticity is primarily driven by changes in the shape and number of dendrites and dendritic spines [57–60]. Chronic administration of opioids can lead to reduction in the spine density [61]. In addition to the drug-induced plasticity, regulation of the cytoskeleton alterations may be influenced by mutations in the genes encoding the cytoskeleton proteins [55].
