Patterns of brain activation associated with contextual conditioning to methamphetamine in mice

Behav Neurosci. 2005 Jun;119(3):759-71. doi: 10.1037/0735-7044.119.3.759.


Classical conditioning is thought to play a key role in addiction. The authors used c-Fos immunohistochemistry to demonstrate a conditioned physiological response to methamphetamine (meth) in mice. Male outbred mice were placed into an environment where they had previously experienced 2 mg/kg meth or saline. The meth-paired mice displayed increased c-Fos in several brain regions, including the nucleus accumbens, prefrontal cortex, orbitofrontal cortex, basolateral amygdala, and bed nucleus of the stria terminalis. No conditioned locomotor activity was observed, but individual activity levels strongly correlated with c-Fos in many regions. A batch effect among immunohistochemical assays was demonstrated. Results implicate specific brain regions in classical conditioning to meth and demonstrate the importance of considering locomotor activity and batch in a c-Fos study.

Publication types

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

MeSH terms

  • Analysis of Variance
  • Animals
  • Behavior, Animal / drug effects
  • Brain / anatomy & histology
  • Brain / drug effects*
  • Brain / metabolism
  • Brain Mapping
  • Cell Count / methods
  • Central Nervous System Stimulants / pharmacology*
  • Conditioning, Classical / drug effects*
  • Conditioning, Classical / physiology
  • Immunohistochemistry / methods
  • Male
  • Methamphetamine / pharmacology*
  • Mice
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Proto-Oncogene Proteins c-fos / metabolism
  • Time Factors


  • Central Nervous System Stimulants
  • Proto-Oncogene Proteins c-fos
  • Methamphetamine