Ethanol acts synergistically with a D2 dopamine agonist to cause translocation of protein kinase C

Ethanol and other drugs of abuse increase synaptic dopamine levels; however , little is known about how ethanol alters dopaminergic signaling. We have reported that ethanol induces translocation of delta and epsilon protein ki nase C (PKC) in neural cells in culture. Using NG108-15 and Chinese hamster ovary cell lines that express the dopamine D2 receptor (D2R), we show here that the D2R agonist R(-)- 2,10,11-trihydroxy-N-propyl-noraporphine hydrob romide (NPA) also causes translocation of d and epsilon PKC to the same sit es as ethanol-induced translocation. D2R agonist and ethanol-induced transl ocation of delta and epsilon PKC share a common pathway that is blocked by pertussis toxin and requires phospholipase C (PLC) activity. These data sug gest that both D2R agonists and ethanol activate PLC via a trimeric G prote in leading to production of diacylglycerol with subsequent activation and t ranslocation of delta and epsilon PKC. Moreover, ethanol and NPA, when pres ent together at low concentrations that alone are ineffective, act synergis tically to cause translocation of delta and epsilon PKC. Our data suggest t hat ethanol causes translocation of delta and epsilon PKC but cells express ing the D2R, such as neurons in the nucleus accumbens, may be particularly sensitive to low concentrations of ethanol.