Reversal in central nervous system function during ethanol withdrawal in humans and experimental animals

The ultimate objective in devising animal analogs of physical dependence on ethanol is to obtain meaningful imitations that have behavioral and biological similarities to human subjects during the ethanol withdrawal syndrome. The natural history of alcoholic disease in human subject and in experimental animals involves three periods, each characterized on the basis of temporal relationships, pattern of ethanol intake, blood ethanol concentrations, and/or a typical sequence in the onset and decay of the characteristic spectrum and continuum of overt behavioral, neurological, and biological signs and responses. These characteristics are expressions of different functional states of the central nervous system (CNS): 1) the baseline period or predrinking period reflects normal function of the CNS; 2) the induction period or drinking period is characterized by overt signs and responses of nonspecific, long-term CNS depression; and 3) the withdrawal period is characterized by a relatively rapid transition in the CNS function from depression during the prodromal detoxication phase to hyperexcitability observed during the withdrawal syndrome (dependence phase). The rapid transition from overt depression to overt hyperexcitability is a consequence of rapid removal of the drug from the system, and constitutes the basis of the reversal in the CNS function in both humans and experimental animals.