Figure 3.

Possible mechanism for agonist-induced degradation of Gα_olf proteins in striatonigral and striatopallidal MSNs. Glutamate released from the corticostriatal afferents could activate postsynaptic N-methyl-D-aspartate (NMDA) receptors (NMDARs) to increase the extracellular adenosine levels in the striatum. Repeated exposure to levodopa might cause a pulsatile release of DA from the nigrostriatal afferents to activate DA D₁ receptors (D₁Rs) in striatonigral MSNs (D1-cells). This might facilitate the NMDAR-evoked increase in extracellular adenosine release and, thereby, indirectly activate the adenosine A_2A receptors (A_2ARs) in striatopallidal MSNs expressing DA D₂ receptors (D₂Rs; D2-cells). Thus, a usage-induced downregulation of Gα_olf protein levels could occur not only in the striatonigral MSNs but also in striatopallidal MSNs.