Schematic representation of the proposed mechanisms for the in vitro action of cocaine on MOR expression. Cocaine increases NO production and decreases HDAC activity, which could lead to further increases in NO production as well as enhanced MOR protein stability. Multiple repeated treatments with cocaine also lead to increases in the levels of c-fos mRNA. c-Fos can bind to Jun transcription family members to stimulate AP-1 activity, which, in combination with HDAC inhibition, may contribute to an up-regulation in MOR mRNA levels through enhanced transcription. Sites of inhibition (⊥) by curcumin and L-NAME are indicated.