title: The molecular basis of tolerance.
abstract: Tolerance is defined as the diminished response to alcohol or other drugs over the course of repeated or prolonged exposure. This mechanism allows physiological processes to achieve stability in a constantly changing environment. The onset of tolerance may occur within minutes, during a single exposure to alcohol (i.e., acute tolerance), or over longer timeframes and with prolonged exposure to alcohol (i.e., rapid or chronic tolerance). Changes in tolerance induced by alcohol may affect several processes at the molecular, cellular, or behavioral level. These effects often are interrelated and may be difficult to separate. This article describes changes at the molecular level that are related to the onset of acute, rapid, or chronic tolerance. It focuses on neuronal membrane-bound channels and the factors that affect their function and production, such as modification of protein synthesis and activity, interaction with the membrane lipid microenvironment, epigenetic effects on cytoplasmic regulation, and gene transcription. Also considered is the genetics of tolerance.
authors.affiliation: University of Massachusetts Medical School, Worcester, Massachusetts.
authors.forename: Andrzej Z
authors.initials: AZ
authors.lastname: Pietrzykowski
authors.forename: Steven N
authors.initials: SN
authors.lastname: Treistman
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D004361:Drug Tolerance / Q000502:physiology*; D044127:Epigenesis, Genetic / Q000187:drug effects / Q000235:genetics; D000431:Ethanol / Q000008:administration & dosage*; D006801:Humans; D008563:Membrane Lipids / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D008563:Membrane Lipids; D008565:Membrane Proteins; D000431:Ethanol