Among the molecular pathways regulated by cocaine are several not heretofore appreciated in cocaine action. In addition to the sirtuins discussed above, examples include protein ubiquitination, Toll-like receptor signaling, and FGF signaling. Indeed, protein ubiquitination signaling regulates dendritic spine morphology and neuronal function (Pak and Sheng, 2003), and NAC-1, a cocaine-induced gene, can shuttle the proteasome and a ubiquitin ligase into spines in response to neural activity (Shen et al., 2007). While NAC-1 was not regulated at the time point used in our ChIP-chip analyses, many ubiquitin signaling molecules were regulated in response to cocaine and, like NAC-1, now warrant further investigation.
