4.7 Article

Chronic Stress, Drug Use, and Vulnerability to Addiction

Journal

ADDICTION REVIEWS 2008
Volume 1141, Issue -, Pages 105-130

Publisher

WILEY-BLACKWELL
DOI: 10.1196/annals.1441.030

Keywords

chronic stress; early life stress; addiction risk; relapse; craving; mesolimbic dopamine

Funding

  1. National Institutes of Health [P50-DA165556, R01-AA13892, R01-DA18219, U01-RR24925]
  2. NATIONAL CENTER FOR RESEARCH RESOURCES [UL1RR024925] Funding Source: NIH RePORTER
  3. NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM [R01AA013892] Funding Source: NIH RePORTER
  4. NATIONAL INSTITUTE ON DRUG ABUSE [R01DA018219, PL1DA024859] Funding Source: NIH RePORTER

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Stress is a well-known risk factor in the development of addiction and in addiction relapse vulnerability. A series of population-based and epidemiological studies have identified specific stressors and individual-level variables that are predictive of substance use and abuse. Preclinical research also shows that stress exposure enhances drug self-administration and reinstates drug seeking in drug-experienced animals. The deleterious effects of early life stress, child maltreatment, and accumulated adversity on alterations in the corticotropin releasing factor and hypothalamic-pituitary-adrenal axis (CRF/HPA), the extrahypothalamic CRF, the autonomic arousal, and the central noradrenergic systems are also presented. The effects of these alterations on the corticostriatal-limbic motivational, learning, and adaptation systems that include mesolimbic dopamine, glutamate, and gamma-amino-butyric acid (GABA) pathways are discussed as the underlying pathophysiology associated with stress-related risk of addiction. The effects of regular and chronic drug use on alterations in these stress and motivational systems are also reviewed, with specific attention to the impact of these adaptations on stress regulation, impulse control, and perpetuation of compulsive drug seeking and relapse susceptibility. Finally, research gaps in furthering our understanding of the association between stress and addiction are presented, with the hope that addressing these unanswered questions will significantly influence new prevention and treatment strategies to address vulnerability to addiction.

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