Figure 1.

Schematic representation of select cell signaling pathways involved in drug addiction. Activation of cell membrane receptors, such as D1 and Trk receptors, results in the propagation of that signal through multiple intracellular signaling cascades. Specifically, the MAPK and adenylate cyclase/PKA signaling cascades have been shown to be activated via dopaminergic signaling. Ultimately, activation of these intracellular signaling cascades results in gene transcription within the nucleus of the cell. Two of the many downstream gene targets of such signaling are CREB and ΔFosB. Whereas CREB phosphorylation is believed to mediate some of the behavioral plasticity resulting from drugs of abuse, the accumulation of the stable transcription factor ΔFosB is postulated to underlie drug induced structural plasticity. Targets of ΔFosB transcription in turn can affect intrinsic membrane excitability through the insertion of GluR2 subunits into AMPA receptors, as well as structural changes through dendritic spine plasticity via cdk5 activation. Importantly, D2 receptor activation counteracts D1 receptor activation [50].