Induction of a long-lasting AP-1 complex composed of altered Fos-like proteins in brain by chronic cocaine and other chronic treatments

Neuron. 1994 Nov;13(5):1235-44. doi: 10.1016/0896-6273(94)90061-2.


Following chronic cocaine treatment, we have found a long-lasting increase in AP-1 binding in the rat nucleus accumbens and striatum, two important targets of the behavioral effects of cocaine. This increase develops gradually over several days and remains at 50% of maximal levels 7 days after the last cocaine exposure. Supershift experiments, along with one- and two-dimensional Western blots, indicate that this chronic AP-1 complex contains at least four Fos-related antigens (FRAs), some of which display delta FosB-like immunoreactivity, that are induced selectively by chronic, but not acute, cocaine treatment. The same chronic FRAs were also induced by several different types of chronic treatments in a region-specific manner in the brain. Thus, the chronic FRAs and associated chronic AP-1 complex could mediate some of the long-term changes in gene expression unique to the chronic-treated state as opposed to the acute-treated and normal states.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blotting, Western
  • Brain / metabolism*
  • Brain Mapping
  • Cocaine / administration & dosage*
  • Drug Administration Schedule
  • Electrophoresis, Gel, Two-Dimensional
  • Electroshock
  • Isoelectric Point
  • Male
  • Molecular Weight
  • Nucleus Accumbens / metabolism
  • Proto-Oncogene Proteins c-fos / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Seizures / physiopathology
  • Substance-Related Disorders / metabolism
  • Transcription Factor AP-1 / chemistry
  • Transcription Factor AP-1 / metabolism*
  • Tranylcypromine / administration & dosage


  • Proto-Oncogene Proteins c-fos
  • Transcription Factor AP-1
  • Tranylcypromine
  • Cocaine