Addictive drugs can activate PKCs by stimulating dopamine D2, opioid, or cannabinoid receptors, releasing Gβγ from Gi/o, which stimulates PLC to produce DAG and IP3.165 In addition, hetero-oligomers of D1 and D2 dopamine receptors activate Gq,166 which also activates PLC.165 Phospholipase D (PLD) can produce DAG by cleaving phosphatidylcholine into phosphatidic acid (PA) and free choline.167 PA is then converted to DAG by PA phospho-hydrolase. PLD is also activated by many of the same G protein–coupled receptors as PLC, as well as by the small GTPase RhoA and by cPKCs.167
