Possible Role of Microsomal Changes Induced by Ethanol Intake in the Development of Tolerance and Dependence

Abstract

Characteristics of alcoholism include the development of both tolerance and dependence to ethanol. Probably the most significant aspect of ethanol tolerance is increased central nervous system tolerance, that is a progressive decrease in responsiveness of the central nervous system to a given level of alcohol. In addition to this central nervous effect, part of the adaptation is due to increased rates of ethanol metabolism, so called metabolic adaptation. Indeed, it has been found that alcoholics have unusually high rates of ethanol metabolism (Isbell et al., 1955; Kater et al., 1969a). Moreover, experimental ethanol administration results in increased rate of ethanol metabolism, both in man (Misra et al., 1971) and in rats (Hawkins et al., 1966; Lieber and DeCarli, 1970a; Tobon and Mezey, 1971). The mechanism of this acceleration is still the subject of debate. Some of the results to be discussed favor a possible role of microsomal changes induced by ethanol consumption in the development of the metabolic tolerance to ethanol. Similarly, a hypothesis will be presented according to which the microsomal changes may contribute to the development of dependence. Since this theory results from the elucidation of a new pathway for ethanol metabolism, namely the microsomal ethanol oxidizing system (MEOS), a description of the latter will precede the discussion of its contribution to the development of adaptation and dependence.