Common neural adaptations and bidirectional influences of stress and addiction: Recent insights from basic research

Objective: Clinical evidence suggests a complex-perhaps correlative-relationship between stressful experiences and addiction. The goal of this review is to provide an overview of recent basic research linking stress and addiction, to indicate novel areas of study, and to suggest how data from basic research may influence clinical assessment and treatment of patients with stress-related disorders, substance abuse, or a history of both disorders. Methods: Reviewed here are recent basic research (preclinical) articles available via PubMed (www.ncbi.nlm.nih.gov) with particular relevance to novel neural mechanisms underlying the putative stress/addiction relationship. Findings: Three types of relationships between stress and addiction are identified and discussed: (1) Neural adaptations common to both chronic stress and chronic exposure to drugs of abuse; (2) The influence of stress on the rewarding or sensitizing aspects of drugs of abuse; and (3) The influence of stress on the relapse to drug taking after a drug-free period. Each relationship appears to involve alterations in dopaminergic and glutamatergic systems and their related second messenger pathways. However, brain regions that influence the brain's reward pathway, such as the hippocampus, and other novel aspects of neuroplasticity, such as adult neurogenesis, are also receiving attention. Conclusions: A wealth of evidence shows that stress and addiction can produce similar adaptations in discrete brain regions, and that there is bidirectional influence of the experience of stress and drug exposure. These preclinical findings encourage further exploration of the neural mechanisms underlying stress and addiction with the hope that additional discoveries will aid treatment of patients with stress-related disorders and addiction, or comorbid diagnoses.