The mechanisms by which drugs induce tolerance and physical dependence are still largely unknown. Although tolerance and physical dependence are not unique to ethanol, there are distinguishing features. Ethanol, because of its molecular properties, has ubiquitous distribution within an organism. It also appears to affect most metabolic and physiological functions. This multiplicity of effects makes the investigation of the action of ethanol especially difficult.
Most evidence indicates that physical dependence is a central nrevous system phenomena.
The neurochemical basis for tolerance and dependence are being examined using an experimental animal model. More specifically, we have been examining the involvement of monamine neurotransmitters in ethanol tolerance and physical dependence in rats. We are using both in vivo and in vitro techniques for this purpose. Physiological and pharmacological approaches are used to correlate with the neurochemical changes occurring during the development of tolerance and withdrawal from ethanol. Again, rats are used as experimental subjects.