title: Genetic and environmental influences on ethanol consumption: perspectives from preclinical research.
abstract: BACKGROUND
  Alcohol use disorders (abuse and dependence, AUD) are multifactorial phenomena, depending on the interplay of environmental and genetic variables.
  
  
  METHODS
  This review describes current developments in animal research that may help (a) develop gene therapies for the treatment of alcoholism, (b) understand the permissive role of stress on ethanol intake, and (c) elucidate why exposure to ethanol early in life is associated with a greater risk of AUD.
  
  
  RESULTS
  The polymorphisms found in liver alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) affect the elimination of ethanol and the susceptibility to ethanol intake. A highly active ADH protects against alcoholism, an effect related to a presteady state burst in arterial acetaldehyde. Social stressors, such as repeated early maternal separation or social defeat, exert a permissive effect on ethanol intake, perhaps by altering the normal development of the hypothalamic-pituitary-adrenal axis. Ethanol exposure during gestation, infancy, or adolescence increases the likelihood of AUD later in life. Early perception of ethanol's positive and negative (anti-anxiety) reinforcing effects may play a role in this phenomenon.
  
  
  CONCLUSIONS
  The review underscores the advantages of using preclinical animal models of AUD and highlights points of intersection between the topics to help design a more integrated approach for the study of alcohol-related problems.
authors.affiliation: Instituto de Investigaciones Médicas M. y M. Ferreyra (INIMEC-CONICET), Argentina. rpautassi@gmail.com
authors.forename: Ricardo M
authors.initials: RM
authors.lastname: Pautassi
authors.forename: Rosana
authors.initials: R
authors.lastname: Camarini
authors.forename: Isabel Marian
authors.initials: IM
authors.lastname: Quadros
authors.forename: Klaus A
authors.initials: KA
authors.lastname: Miczek
authors.forename: Yedy
authors.initials: Y
authors.lastname: Israel
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics* / Q000523:psychology / Q000628:therapy; D019973:Alcohol-Related Disorders / Q000235:genetics* / Q000523:psychology / Q000628:therapy; D000818:Animals; D004777:Environment; D015316:Genetic Therapy; D023421:Models, Animal; D012307:Risk Factors; D013315:Stress, Psychological