Activation of NMDA receptors in the nucleus accumbens and hippocampus following the reactivation of cocaine-contextual memories stimulates a protein phosphatase cascade, through PP2B and PP1, resulting in dephosphorylation of Akt and GSK-3β. GSK-3β can regulate mTORC1 and CREB. Arrows indicate changes in enzyme activity following reactivation of cocaine-associated memories. GSK, glycogen synthase kinase; mTORC1, mammalian target of rapamycin complex 1; PI3K, phosphatidylinositol 3-kinase; PP1, protein phosphatase 1; PP2B, protein phosphatase 2B. CREB, cAMP response element-binding protein. Adapted from Shi et al., 2014 & 2019b.