Fig. 2. Lithium, amphetamine-related sensitization, and cell-clearing systems.

Lithium inhibits IMPase and IPPase, as well as PKC and GSK3β, which are triggered downstream of dopamine GPCRs. This results in reduced production and phospho-tau/misfolded proteins and the rescue of cell-clearing systems, which are impaired by mTOR hyperactivation placed downstream of D1 DA receptors and/or by abnormal amounts of phospho-tau. At the same time, lithium disassembles the GSK3-β-activating proteins β-ARR and PP2A from the complex they form with GPCRs/AKT meanwhile targeting them for degradation by the cell-clearing systems. In this way, lithium adjusts dopamine imbalances that occur following psychostimulant intake/administration and abnormal activation of GPCRs and related downstream signaling pathways.