Learning mechanisms of drug dependence

The development of drug dependence relies heavily on an aberrant learning history. Initially, the experience of the drug itself is linked with environmental cues through a process of Pavlovian conditioning. The unconditioned drug stimulus becomes associated with conditioned stimuli that can then come to instigate goal-directed drug seeking. Over time, a shift in the circuitry maintaining the drug-seeking behaviour occurs. This transition from a dominant role of the mesolimbic dopamine system to the nigrostriatal dopamine system is reflected behaviourally in a transition to habitual drug seeking. At this stage, the drug-seeking behaviour is resistant to devaluation of the drug stimulus, indicating a loss of outcome value as the dominate source of motivation, and instead implicating the drug-associated conditioned stimulus as the driving force of the behaviour. From a clinical standpoint, increased focus on the impact of associated environmental cues in perpetuating drug habits should be of use. Unfortunately, approaches utilizing extinction processes such as cue-exposure therapy have been less than successful in prolonging abstinence. One of the factors that may contribute to that is our often narrow approach to understanding the role of the drug itself. Importantly, a drug is not only a rewarding Pavlovian unconditioned stimulus or operant reinforcer. The drug experience can also function as a conditioned stimulus, indicating the presence of another appetitive environmental stimulus, as well as set occasions for when other conditioned-unconditioned stimulus associations are available. Combined, understanding the functional significance of the impact on neural processes of the drug experience in various learning domains will provide a more solid foundation for moving forward in the development of treatment techniques.