Environmental modulation of amphetamine-induced c-fos expression in D1 versus D2 striatal neurons

Behav Brain Res. 1999 Sep;103(2):203-9. doi: 10.1016/s0166-4328(99)00041-8.


We have reported previously that exposure to environmental novelty enhances the behavioral activating effects of amphetamine and its ability to induce the immediate early gene c-fos in the striatum and in other brain regions. In the present study, we used double in situ hybridization histochemistry to study the effect of amphetamine and/or novelty on c-fos expression in two populations of striatal neurons that preferentially express either D1 or D2 dopamine receptor mRNA. When given intraperitoneally to rats in their home cage, amphetamine (2.0 mg/kg) increased c-fos expression only in D1 neurons. In contrast, when the same dose of amphetamine was administered to rats in a novel environment, c-fos was increased in both D1 and D2 neurons. We conclude that the neural populations engaged by amphetamine vary as a function of the circumstances surrounding its administration.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amphetamine / pharmacology*
  • Animals
  • Dopamine Uptake Inhibitors / pharmacology*
  • Environment*
  • Gene Expression / drug effects*
  • Genes, fos / drug effects*
  • In Situ Hybridization
  • Male
  • Neurons / drug effects
  • Neurons / physiology*
  • Oxidopamine / pharmacology
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D1 / drug effects*
  • Receptors, Dopamine D2 / drug effects*
  • Sympatholytics / pharmacology


  • Dopamine Uptake Inhibitors
  • RNA, Messenger
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Sympatholytics
  • Oxidopamine
  • Amphetamine