PKA can contribute to drug-induced synaptic plasticity. PKA phosphorylates GluR1 subunits of AMPA receptors, which promotes AMPA receptor trafficking to the cell surface.77 Dopamine D1 receptor agonists, SKF81297 and SCH23390, and the PKA activator Sp-cAMPS increase GluR1 cell surface expression in the NAc78 and the hippocampus of rats.79 Drug-induced activation of PKA can thus increase synaptic strength, measured electrophysiologically as an increase in the ratio of AMPA- to NMDA-mediated current. This provides a mechanism for drug-induced synaptic plasticity. In addition to AMPA currents, PKA can also regulate NMDA-stimulated currents. In rat midbrain slices, acute treatment with cocaine produces a delayed increase in NMDA-mediated currents in VTA dopaminergic neurons that is blocked by the PKA inhibitor Rp-cAMPS and by D1/D5 receptor antagonists.80
