Dynamic BDNF activity in nucleus accumbens with cocaine use increases self-administration and relapse

Nat Neurosci. 2007 Aug;10(8):1029-37. doi: 10.1038/nn1929. Epub 2007 Jul 8.


A single exposure to cocaine rapidly induces the brief activation of several immediate early genes, but the role of such short-term regulation in the enduring consequences of cocaine use is poorly understood. We found that 4 h of intravenous cocaine self-administration in rats induced a transient increase in brain-derived neurotrophic factor (BDNF) and activation of TrkB-mediated signaling in the nucleus accumbens (NAc). Augmenting this dynamic regulation with five daily NAc BDNF infusions caused enduring increases in cocaine self-administration, and facilitated relapse to cocaine seeking in withdrawal. In contrast, neutralizing endogenous BDNF regulation with intra-NAc infusions of antibody to BDNF subsequently reduced cocaine self-administration and attenuated relapse. Using localized inducible BDNF knockout in mice, we found that BDNF originating from NAc neurons was necessary for maintaining increased cocaine self-administration. These findings suggest that dynamic induction and release of BDNF from NAc neurons during cocaine use promotes the development and persistence of addictive behavior.

Publication types

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

MeSH terms

  • Analysis of Variance
  • Anesthetics, Local / administration & dosage*
  • Animals
  • Behavior, Animal / drug effects
  • Brain-Derived Neurotrophic Factor / deficiency
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Cocaine / administration & dosage*
  • Cocaine-Related Disorders / metabolism
  • Cocaine-Related Disorders / physiopathology
  • Conditioning, Operant / drug effects
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation / drug effects*
  • Male
  • Mice
  • Mice, Knockout
  • Motor Activity / drug effects
  • Neurons / drug effects
  • Neurons / metabolism
  • Nucleus Accumbens / cytology
  • Nucleus Accumbens / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, trkB / metabolism
  • Reinforcement, Psychology*
  • Self Administration / methods
  • Time Factors


  • Anesthetics, Local
  • Brain-Derived Neurotrophic Factor
  • Receptor, trkB
  • Cocaine