Components of drug dependence: reinforcement, discrimination and adaptation

A general scheme of addiction should attempt to provide a unifying framework that links together the many dimensions of the problem. Dependence is manifested in the molecular, cellular and neural systems, and at the behavioural, cognitive and social levels. The approach presented in this paper regards drug-seeking behaviour as the main common element in all drug addictions and sees changes in this behaviour as the ultimate end-point for preventative and therapeutic measures. The multifactor model (Fig. 1) stresses the importance of rewarding, discriminative and aversive effects of drugs that interact with genetic and environmental factors to produce drug-seeking behaviour. The analysis of these effects can extend to studies not only of the psychological mechanisms, but also of associated neural mechanisms in terms of neurochemistry and neuroanatomy. Drug-seeking behaviour involves repeated exposure to drugs that produce further adaptive changes that regulate subsequent intake. Studies on behavioural tolerance and sensitization show that the adaptive changes cannot be considered in isolation because the extent and nature of adaptation depends on the circumstances in which drugs are given. For example, environmental stimuli that have been associated with drug action in the past can exert a profound influence on individual reactions to addictive drugs. The model portrays the reinforcing and other related stimulus properties of drugs as malleable effects determined by many factors, from which it follows that the neurobiology of dependence is not the neurobiology of either acute or chronic exposure to drugs; it is the neurobiology of both single and repeated exposure to drugs under environmental and genetic conditions that lead to or are accompanied by drug-seeking behaviour.