Since calmodulin has been hypothesized to be a central integrator of synaptic plasticity [27] and modulates the activity and calcium-sensitivity of key signaling molecules, such as AC, CAMKII and IV (CAMKIV), and the Ras-MAPK signaling pathway, this effect could significantly impact a number of downstream signaling pathways. One such target is CAMKII, which is critical for the establishment of synaptic plasticity and memory and in stabilizing dendritic architecture [28], with a specific role for CAMKIIB in targeting the alpha CAMKII isoform to dendritic spines and the cell cortex [29]. The significant decrease in CALM1, CALM2 and CAMKIIB transcripts suggest that altered regulation of neuroplasticity and dendritic architecture by calmodulin-regulated pathways could be a common theme in human abuse of cocaine, cannabis and/or phencyclidine.
