Fig. 1.

Crosstalk between the different mechanisms underlying the modulation of NSPCs. The mechanisms by which morphine, cocaine and methamphetamine (METH) modulate adult NSPCs exemplify the crosstalk between the MAPK cascade, cell cycle regulation and miRNA expression induced by addictive drugs. Morphine up-regulates miR-181a by the ERK/TRBP/Dicer pathway. MiR-181a further controls Prox1/Notch1 signaling, which ultimately results in alterations of NSPC differentiation. Cocaine activates the miR-9/TLX loop, which in turn regulates p21 and further interferes with the effects of cell cycle regulatory molecules that alter proliferation and differentiation of NSPCs. On the other hand, cocaine up-regulates miR-124, which inhibits Notch1 expression, which results in cell cycle arrest. Methamphetamine activates the p53/p21 cascade, which blocks the effects of cell cycle regulatory molecules, resulting in the decreased proliferation and increased neuronal differentiation of NSPCs