Biological basis of drug-induced tolerance, rebound, and dependence. Contribution of recent research on benzodiazepines.

It is proposed that the general biological basis of acquired drug tolerance, of rebound phenomena induced by drugs, and of physiological dependence is a drug-induced adaptive syndrome. Several examples of the compensatory molecular, cellular and system responses are presented that may be induced by the primary drug-induced perturbation in the base-line of various neuronal and non-neuronal activities. Some form of adaptive syndrome is the inevitable consequence of the reciprocal interaction between most or all major classes of drugs and the organism. Knowledge of the molecular and cellular targets of drugs provides an understanding of the various phenomena of the drug-induced adaptive syndrome as well as of the means to avoid or attenuate their potential danger for subjects chronically exposed to drugs. Psychological dependence is discussed as a further factor which, in combination with drug-induced adaptive changes, facilitates drug abuse and, in particular, addiction or drug-seeking behavior. The phenomena of the adaptive syndrome induced by benzodiazepines are discussed against the background of medical science's present advanced knowledge of the molecular and synaptic mechanisms of action of this class of drugs.