The pathways exhibiting sustained changes were examined in more detail. Unique sets of cadherins and protocadherins appeared in each Cluster (Table 3). While many cadherins and protocadherins showed a sustained increase in expression (Cluster i), others increased only in Withdrawal (Cluster ii) or showed a transient response to Cocaine (Clusters iii and iv). The clustered families of protocadherins, Pcdhα, -β, and γ, are important in neuronal development and are synaptically enriched in mature myelinated neurons (Morishita and Yagi, 2007). The Pcdhβ gene cluster includes 22 genes; three showed a sustained increase (Cluster i), five were increased only after Withdrawal (Cluster ii), five exhibited an increase only after Cocaine (Cluster iii), and one showed a sustained decrease in expression (Cluster v). In contrast, the Pcdhγ cluster of 23 genes exhibited a more homogeneous expression pattern in which expression of all 21 detected isoforms showed a sustained decrease (Cluster v).
