Using c-fos to study neuronal ensembles in corticostriatal circuitry of addiction

Brain Res. 2015 Dec 2;1628(Pt A):157-73. doi: 10.1016/j.brainres.2014.11.005. Epub 2014 Nov 11.


Learned associations between drugs and environment play an important role in addiction and are thought to be encoded within specific patterns of sparsely distributed neurons called neuronal ensembles. This hypothesis is supported by correlational data from in vivo electrophysiology and cellular imaging studies in relapse models in rodents. In particular, cellular imaging with the immediate early gene c-fos and its protein product Fos has been used to identify sparsely distributed neurons that were strongly activated during conditioned drug behaviors such as drug self-administration and context- and cue-induced reinstatement of drug seeking. Here we review how Fos and the c-fos promoter have been employed to demonstrate causal roles for Fos-expressing neuronal ensembles in prefrontal cortex and nucleus accumbens in conditioned drug behaviors. This work has allowed identification of unique molecular and electrophysiological alterations within Fos-expressing neuronal ensembles that may contribute to the development and expression of learned associations in addiction.

Keywords: Conditioned cues; Daun02 inactivation; Drug environment; Extinction; Nucleus accumbens; Prefrontal cortex; Self-administration.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Animals
  • Behavior, Addictive / metabolism*
  • Neural Pathways / metabolism
  • Neurons / metabolism*
  • Nucleus Accumbens / metabolism*
  • Prefrontal Cortex / metabolism*
  • Proto-Oncogene Proteins c-fos / metabolism*
  • Substance-Related Disorders / metabolism*


  • Proto-Oncogene Proteins c-fos