The alcohol withdrawal syndrome. A view from the laboratory

Animal models of the alcohol-dependent state, now readily available in many species, show that a withdrawal reaction can be produced whenever intoxication has been continuously maintained, even for short periods of time. The development of the tolerant/dependent state resembles a physiological adaptation in two ways: (1) the animal is no longer much affected by the drug, and (2) withdrawal reveals a condition of CNS hyperexcitability that is the opposite of the primary drug effect. This adaptation is believed to arise in response to ethanol's disordering effect in cell membranes (increased membrane fluidity). Spectrometric techniques such as electron spin resonance and fluorescence polarization reveal that cell membranes of ethanol-withdrawn animals are often abnormally rigid and resistant to ethanol-induced disorder, and it is thought that these changes may correspond to physical dependence and tolerance, respectively. Alterations in the chemical composition of the membranes can often (but not always) explain the abnormal physical properties. The relation between membrane order and ethanol-induced behavioral states is not known in detail, but these observations form a basis for a rational picture of the biochemical changes responsible for the withdrawal syndrome.