title: Protracted abstinence from distinct drugs of abuse shows regulation of a common gene network.
abstract: Addiction is a chronic brain disorder. Prolonged abstinence from drugs of abuse involves dysphoria, high stress responsiveness and craving. The neurobiology of drug abstinence, however, is poorly understood. We previously identified a unique set of hundred mu-opioid receptor-dependent genes in the extended amygdala, a key site for hedonic and stress processing in the brain. Here we examined these candidate genes either immediately after chronic morphine, nicotine, Δ9-tetrahydrocannabinol or alcohol, or following 4 weeks of abstinence. Regulation patterns strongly differed among chronic groups. In contrast, gene regulations strikingly converged in the abstinent groups and revealed unforeseen common adaptations within a novel huntingtin-centered molecular network previously unreported in addiction research. This study demonstrates that, regardless the drug, a specific set of transcriptional regulations develops in the abstinent brain, which possibly contributes to the negative affect characterizing protracted abstinence. This transcriptional signature may represent a hallmark of drug abstinence and a unitary adaptive molecular mechanism in substance abuse disorders.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM and CNRS, Illkirch-Graffenstaden, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Le Merrer
authors.forename: Katia
authors.initials: K
authors.lastname: Befort
authors.forename: Olivier
authors.initials: O
authors.lastname: Gardon
authors.forename: Dominique
authors.initials: D
authors.lastname: Filliol
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Darcq
authors.forename: Doulaye
authors.initials: D
authors.lastname: Dembele
authors.forename: Jerome A J
authors.initials: JA
authors.lastname: Becker
authors.forename: Brigitte L
authors.initials: BL
authors.lastname: Kieffer
mesh_terms: D000679:Amygdala / Q000187:drug effects; D000818:Animals; D016739:Behavior, Addictive / Q000235:genetics / Q000503:physiopathology*; D001921:Brain / Q000187:drug effects*; D016000:Cluster Analysis; D004195:Disease Models, Animal; D013759:Dronabinol / Q000008:administration & dosage; D000431:Ethanol / Q000008:administration & dosage; D015870:Gene Expression / Q000187:drug effects* / Q000235:genetics; D053263:Gene Regulatory Networks / Q000187:drug effects* / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000008:administration & dosage; D009538:Nicotine / Q000008:administration & dosage; D025341:Principal Component Analysis; D060888:Real-Time Polymerase Chain Reaction; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000235:genetics; D013375:Substance Withdrawal Syndrome / Q000235:genetics / Q000503:physiopathology*; D019966:Substance-Related Disorders / Q000235:genetics / Q000503:physiopathology*; D013695:Temperance; D013995:Time; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics
chemical_list: D017450:Receptors, Opioid, mu; D000431:Ethanol; D009538:Nicotine; D009020:Morphine; D013759:Dronabinol