Ethanol dependence in the rat: role of extrapyramidal motor systems in the withdrawal reaction

Rats were implanted with chronic recording electrodes in the caudate nucleus, substantia nigra, red nucleus, and pontine reticular formation and thereafter maintained on ethanol-containing liquid diets for 18 to 22 days. The removal of ethanol resulted in the time-dependent appearance of epileptiform abnormalities in each of the explored brain regions. The abnormalities characteristically began with increases in EEG synchrony and amplitude coupled with the appearance of epileptiform spike activity, which increased in amplitude and frequency during the latter stages of withdrawal. Quantification of preconvulsive epileptiform spike activity revealed major differences in the temporal sequence of development of spiking in the caudate nucleus and substantia nigra compared to the red nucleus and pontine reticular formation. However, a significant equipotentiality existed among these regions as initiation sites for seizure discharge during spontaneous behavioral convulsion. It was concluded that these brain sites, which have previously been considered to serve significant motor functions, play an active, but as yet unspecifiable, role in the genesis of the ethanol withdrawal reaction. It was further hypothesized that an important aspect of the development of epileptiform activity during the ethanol withdrawal reaction may involve interaction of the caudate nucleus, substantia nigra, and red nucleus with existing thalamocortical synchronizing systems in the midline and nonspecific thalamic nuclei.