Drug-induced adaptation in the catecholamine systems: on the inevitability of sensitization

The behavioral and psychological effects of psychoactive drugs cannot be reduced to the straightforward consequences of ligand–receptor binding: attempts to do so neglect the complexity of drug actions. The importance of this issue is illustrated by a series of studies indicating that the environmental context can exert a powerful modulatory influence on the ability of drugs to induce neuroplastic adaptations in brain areas implicated in drug addiction. Thus, an understanding of how repeated drug use sometimes leads to addiction will also require considering the environment in which drugs are experienced.