title: Alcohol: a stimulant activating brain stress responsive systems with persistent neuroadaptation.
abstract: Addictive diseases, including addiction to alcohol, opiates or cocaine, pose massive public health costs. Addictions are chronic relapsing brain diseases, caused by drug-induced direct effects and persistent neuroadaptations at the molecular, cellular and behavioral levels. These drug-type specific neuroadapations are mainly contributed by three factors: environment, including stress, the direct reinforcing effects of the drug on the CNS, and genetics. Results from animal models and basic clinical research (including human genetic study) have shown important interactions between the stress responsive systems and alcohol abuse. In this review we will discuss the involvement of the dysregulation of the stress responsive hypothalamic-pituitary-adrenal (HPA) axis in alcohol addiction (Section I). Addictions to specific drugs such as alcohol, psychostimulants and opiates (e.g., heroin) have some common direct or downstream effects on several brain stress-responsive systems, including vasopressin and its receptor system (Section II), POMC and mu opioid receptor system (Section III) and dynorphin and kappa opioid receptor systems (Section IV). Further understanding of these systems, through laboratory-based and translational studies, have the potential to optimize early interventions and to discover new treatment targets for the therapy of alcoholism. This article is part of the Special Issue entitled 'CNS Stimulants'.
authors.affiliation: Laboratory of the Biology of Addictive Diseases, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Laboratory of the Biology of Addictive Diseases, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA. Electronic address: kreek@rockefeller.edu.
authors.forename: Mary Jeanne
authors.initials: MJ
authors.lastname: Kreek
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D013315:Stress, Psychological / Q000503:physiopathology
chemical_list: D000697:Central Nervous System Stimulants; D000431:Ethanol
keywords: Dynorphin; HPA axis; Kappa opioid receptor; Mu opioid receptor; POMC; V1b receptor; Vasopressin