Ethanol inhibition of adenosine uptake increases extracellular adenosine levels, which activates adenosine receptors. After prolonged exposure to ethanol it takes 12-16 hours after ethanol withdrawal for PKA C a to leave the nucleus and return to the Golgi. The molecular events that mediate prolonged PKA C a translocation are under active study. We are investigating the possibility that PKA C a is retained in the nucleus for long periods of time because chronic ethanol promotes the synthesis of a special intranuclear binding protein, which, in part, maintains intranuclear localization of PKA C a . These results are very similar to findings by Kandel and colleagues characterizing molecular events in early and late stages of learning and memory.
Dopamine is implicated in behavioral responses to all addicting drugs.
Dopaminergic activity in the nucleus accumbens appears to play a major role in craving, satisfaction, reward, and reinforcement of drug-seeking behavior. Neurons in the nucleus accumbens express dopamine D2 and adenosine A2 receptors in the same cells. Therefore, we defined the interaction of D2 and A2 receptors in mediating ethanol responses in stable NG108-15 cell lines transfected with dopamine D2 receptors. We also study primary neuronal cultures. We find that dopamine D2 receptor activation also induces PKA translocation.