Goldstein D B
Drug Alcohol Depend. 1979 Jan-Mar;4(1-2):33-42. doi: 10.1016/0376-8716(79)90039-5.
The homeostat hypothesis of drug addiction states that tolerance and physical dependence may both represent adaptive processes, the body's responses to drugs that change the internal milieu. This conceptual framework inextricably links physical dependence with functional tolerance. Dependence may arise by multiple mechanisms, so that different signs, such as body temperature or CNS excitability, may show different degrees of dependence or may have different time courses. Tolerance may be similarly diverse. It is difficult to test whether tolerance and dependence have the same time course because it is hard to find exactly equivalent signs for such a test. The discrepant data from different laboratories on the rate of recovery from physical dependence may be due to the use of different withdrawal signs as indices. Dissociation of tolerance and dependence has been reported in mice treated with 6-hydroxydopamine, where dependence develops without evidence of tolerance. Conversely, tolerance without expression of dependence is seen in experiments on membranes and synapses in vitro. Changes in lipid composition of cell membranes may explain some kinds of tolerance.
药物成瘾的稳态假说认为，耐受性和身体依赖性可能都代表适应性过程，即身体对改变内环境的药物的反应。这一概念框架将身体依赖性与功能性耐受性紧密联系在一起。依赖性可能通过多种机制产生，因此不同的体征，如体温或中枢神经系统兴奋性，可能表现出不同程度的依赖性，或者可能有不同的时间进程。耐受性也可能同样具有多样性。很难测试耐受性和依赖性是否具有相同的时间进程，因为很难找到用于此类测试的完全等效的体征。不同实验室关于身体依赖性恢复速率的不一致数据可能是由于使用了不同的戒断体征作为指标。在用6-羟基多巴胺处理的小鼠中，已报道耐受性和依赖性的分离，其中依赖性发展而无耐受性证据。相反，在体外膜和突触实验中可以看到无依赖性表现的耐受性。细胞膜脂质组成的变化可能解释某些类型的耐受性。
