Direct Interaction of PP2A Phosphatase with GABA Receptors Alters Functional Signaling.

Addictive drugs usurp the brain's intrinsic mechanism for reward, leading to compulsive and destructive behaviors. In the ventral tegmental area (VTA), the center of the brain's reward circuit, GABAergic neurons control the excitability of dopamine (DA) projection neurons and are the site of initial psychostimulant-dependent changes in signaling. Previous work established that cocaine/methamphetamine exposure increases protein phosphatase 2A (PP2A) activity, which dephosphorylates the GABAR2 subunit, promotes internalization of the GABA receptor (GABAR) and leads to smaller GABAR-activated G-protein-gated inwardly rectifying potassium (GIRK) currents in VTA GABA neurons.