Panther Pathway analysis identified cocaine-regulated changes in the repertoire of intracellular signaling proteins downstream of the regulated Gαi and Gαs-coupled GPCRs (Table 3 and Figure 3). The diagram in Figure 3 depicts the complex interplay of intracellular signaling proteins. For example, only two members of the Mus arrestin gene family are expressed outside of the retina (Kovacs et al., 2009); Arrb1 showed a sustained increase in expression (Cluster i) while Arrb2 exhibited a sustained decrease (Cluster v). Transcripts encoding the β- and γ-subunits of heterotrimeric G-proteins were primarily identified in Cluster v (sustained decrease). In contrast, Regulators of G-protein signaling (RGS genes) appeared in all clusters. Transcripts encoding four adenylate cyclase genes showed a sustained increase in expression (Cluster i) while the transcripts encoding two additional adenylate cyclase genes demonstrated increased expression only in the Withdrawal group (Cluster ii).
