Protracted abstinence from distinct drugs of abuse shows regulation of a common gene network

Addict Biol. 2012 Jan;17(1):1-12. doi: 10.1111/j.1369-1600.2011.00365.x. Epub 2011 Sep 28.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / drug effects
  • Animals
  • Behavior, Addictive / genetics
  • Behavior, Addictive / physiopathology*
  • Brain / drug effects*
  • Cluster Analysis
  • Disease Models, Animal
  • Dronabinol / administration & dosage
  • Ethanol / administration & dosage
  • Gene Expression / drug effects*
  • Gene Expression / genetics
  • Gene Regulatory Networks / drug effects*
  • Gene Regulatory Networks / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Morphine / administration & dosage
  • Nicotine / administration & dosage
  • Principal Component Analysis
  • Real-Time Polymerase Chain Reaction
  • Receptors, Opioid, mu / drug effects
  • Receptors, Opioid, mu / genetics
  • Substance Withdrawal Syndrome / genetics
  • Substance Withdrawal Syndrome / physiopathology*
  • Substance-Related Disorders / genetics
  • Substance-Related Disorders / physiopathology*
  • Temperance
  • Time
  • Transcriptional Activation / drug effects
  • Transcriptional Activation / genetics


  • Receptors, Opioid, mu
  • Ethanol
  • Nicotine
  • Morphine
  • Dronabinol