Increased dihydropyridine-sensitive calcium channels in rat brain may underlie ethanol physical dependence.

Ethanol physical dependence can be viewed as a state of latent hyperexcitability in brain which is exposed on withdrawal of the drug. This hyperexcitability may reflect an increased sensitivity to Ca2+ of central neurones. Dihydropyridine (DHP) binding sites which represent a subtype of neuronal Ca2+-channel, are increased in brains from ethanol-dependent rats as are functional effects of the DHP Ca2+-channel activator, BAYK8644. These effects are reversed by DHP Ca2+ inhibitors, which also prevent the ethanol physical withdrawal syndrome. These results suggest that an increase in DHP-sensitive Ca2+-channels on central neurons may represent the molecular basis for ethanol physical dependence.