Expression of c-Fos protein immunoreactivity in rat brain during ethanol withdrawal is prevented by nifedipine.

Male rats were made physically dependent on ethanol by inhalation of the vapour for 10 days, and c-Fos protein-like immunoreactivity was visualised in the brain of these animals after various periods of ethanol withdrawal. Immunostaining for c-Fos appeared 2 h after ethanol withdrawal, the number of cells increased significantly at 8 h, but c-Fos had returned to basal level after 24 h. Immunoreactive cells were distributed throughout the brain but were concentrated in cerebral cortex, striatum, and hippocampus. Intraperitoneal injection of the calcium channel antagonist nifedipine (3 x 100 mg/kg) prior to, and during ethanol withdrawal totally prevented c-Fos protein-like expression. These results suggest that the superinduction of c-Fos protein in the brain of rats undergoing ethanol withdrawal is induced by calcium influx into neuronal cells, and may be related to previously reported increases in L-type voltage-operated calcium channels in the brain associated with ethanol dependence.