title: Clock genes × stress × reward interactions in alcohol and substance use disorders.
abstract: Adverse life events and highly stressful environments have deleterious consequences for mental health. Those environmental factors can potentiate alcohol and drug abuse in vulnerable individuals carrying specific genetic risk factors, hence producing the final risk for alcohol- and substance-use disorders development. The nature of these genes remains to be fully determined, but studies indicate their direct or indirect relation to the stress hypothalamo-pituitary-adrenal (HPA) axis and/or reward systems. Over the past decade, clock genes have been revealed to be key-players in influencing acute and chronic alcohol/drug effects. In parallel, the influence of chronic stress and stressful life events in promoting alcohol and substance use and abuse has been demonstrated. Furthermore, the reciprocal interaction of clock genes with various HPA-axis components, as well as the evidence for an implication of clock genes in stress-induced alcohol abuse, have led to the idea that clock genes, and Period genes in particular, may represent key genetic factors to consider when examining gene × environment interaction in the etiology of addiction. The aim of the present review is to summarize findings linking clock genes, stress, and alcohol and substance abuse, and to propose potential underlying neurobiological mechanisms.
authors.affiliation: Institute of Psychopharmacology, Central Institute for Mental Health, Medical Faculty of Mannheim, Heidelberg University, Mannheim, Germany; SRI International, Center for Neuroscience, Biosciences Division, Menlo Park, CA, USA. Electronic address: stephanie.perreau-lenz@sri.com.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Perreau-Lenz
authors.affiliation: Institute of Psychopharmacology, Central Institute for Mental Health, Medical Faculty of Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Spanagel
mesh_terms: D000437:Alcoholism / Q000378:metabolism*; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology; D057906:Circadian Clocks / Q000187:drug effects / Q000235:genetics*; D056925:Circadian Rhythm Signaling Peptides and Proteins / Q000187:drug effects / Q000235:genetics*; D003042:Cocaine / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D059647:Gene-Environment Interaction; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism*; D012201:Reward; D013315:Stress, Psychological / Q000378:metabolism*; D019966:Substance-Related Disorders / Q000378:metabolism
chemical_list: D002492:Central Nervous System Depressants; D056925:Circadian Rhythm Signaling Peptides and Proteins; D018765:Dopamine Uptake Inhibitors; D018722:Nicotinic Agonists; D000431:Ethanol; D009538:Nicotine; D003042:Cocaine
keywords: Alcohol; Circadian clock; Cocaine; HPA axis; Nicotine; Period genes