Prevention and treatment of drug addiction by environmental enrichment.

Environmental enrichment (EE) has been shown to have powerful beneficial effects on a variety of physiological and pathological processes. Accumulating evidence indicates that EE can mimic positive life experiences and prevent the development of drug addiction. More recently, EE has also been shown to eliminate already developed addiction-related behaviors and to reduce the risks of relapse. These preventive and "curative" effects of EE are associated with dramatic plastic changes in several brain areas such as the hippocampus, the frontal cortex and the striatum. EE alters neurotransmitter systems, produces changes in gene expression and transcription factors, induces chromatin rearrangement, and stimulates hippocampal neurogenesis. Here we review the existent literature on behavioral, neurochemical, cellular and molecular effects of EE and we discuss different possible ways in which EE-induced neuroadaptations result in decreased vulnerability to addiction and relapse. We propose a unified theoretical framework in which EE is seen as a functional opposite of stress. On the one hand, the antistress effects of EE would reduce the reinforcing effects of drugs and their ability to induce long-lasting neuroplastic changes and, thus, they would prevent the development of drug addiction. On the other hand, permanent or transient restoration of the normal, pre-drug functioning of the stress system would facilitate resisting prepotent desire to take drug and it would decrease the risks of relapse. This theoretical framework highlights the importance of stress in each phase of drug addiction and strongly suggests that life conditions of abstinent addicts should be considered as part of their treatment.