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Addictive diseases, including addiction to alcohol, pose massive public health costs. Addiction is a chronic relapsing disease caused by both the direct effects induced by drugs and persistent neuroadaptations at the molecular, cellular, and behavioral levels. These drug-type specific neuroadaptations are brought on largely by the reinforcing effects of drugs on the central nervous system and environmental stressors. Results from animal experiments have demonstrated important interactions between alcohol and stress-responsive systems. Addiction to specific drugs such as alcohol, psychostimulants, and opioids shares some common direct or downstream effects on the brain's stress-responsive systems, including arginine vasopressin and its V1b receptors, dynorphin and the κ -opioid receptors, pro-opiomelanocortin/ β -endorphin and the μ -opioid receptors, and the endocannabinoids. Further study of these systems through laboratory-based and translational research could lead to the discovery of novel treatment targets and the early optimization of interventions (for example, combination) for the pharmacologic therapy of alcoholism.

Involvement of Activated Brain Stress Responsive Systems in Excessive and “Relapse” Alcohol Drinking in Rodent Models: Implications for Therapeutics