Effects of Amphetamine and Cocaine Treatment on c-Fos, Jun-B, and Krox-24 Expression in Rats With Intrastriatal Dopaminergic Grafts

Exp Neurol. 1999 Sep;159(1):139-52. doi: 10.1006/exnr.1999.7129.

Abstract

Activation of dopaminergic (DA) transmission by psychostimulants increases c-fos expression. d-Amphetamine-induced c-fos activation is reduced in the neostriatum deprived of DA afferents. Dopaminergic grafts implanted into the denervated neostriatum induce a c-fos hyperexpression when challenged with d-amphetamine, which is correlated with the exaggerated compensation of d-amphetamine-induced rotation. The aim of the present study was to test the generality of this phenomenon and the effects of DA grafts on the expression of three immediate early gene-coded proteins (c-Fos, Jun-B, Krox-24) following a challenge with either d-amphetamine or cocaine. c-fos basal expression was low in the neostriatum and was increased by the administration of psychostimulants. These effects were blocked by the DA lesion and restored by the DA grafts. A c-fos hyperexpression was observed within the grafted neostriatum, which was correlated with the compensation of d-amphetamine- or cocaine-induced rotation. Basal levels of Jun-B- and Krox-24-LI nuclei were high within the neostriatum. Administration of d-amphetamine or cocaine did not influence the expression of these IEG-coded proteins. Jun-B expression was not affected by the surgical procedure. In contrast, lesion of DA afferents of neostriatum decreased Krox-24 basal expression, an effect reversed by the grafts. Thus, the expression of c-fos but not Jun-B or Krox-24 appeared to be a good marker for the rotational behavior exhibited by DA-grafted rats challenged with drugs that increased DA transmission. This generalized c-fos overshoot indicates an abnormal activation of postsynaptic neurons by dopamine and points to its value as an indicator of the deleterious effects of DA grafts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies
  • Behavior, Animal / drug effects
  • Brain Tissue Transplantation*
  • Cocaine / pharmacology*
  • DNA-Binding Proteins / analysis
  • DNA-Binding Proteins / biosynthesis*
  • DNA-Binding Proteins / immunology
  • Dextroamphetamine / pharmacology*
  • Dopamine / physiology
  • Dopamine Uptake Inhibitors / pharmacology*
  • Early Growth Response Protein 1
  • Fetal Tissue Transplantation*
  • Graft Survival
  • Immediate-Early Proteins*
  • Male
  • Neostriatum / surgery
  • Neurons / chemistry
  • Neurons / metabolism
  • Neurons / transplantation*
  • Proto-Oncogene Proteins c-fos / analysis
  • Proto-Oncogene Proteins c-fos / biosynthesis
  • Proto-Oncogene Proteins c-fos / immunology
  • Proto-Oncogene Proteins c-jun / analysis
  • Proto-Oncogene Proteins c-jun / biosynthesis
  • Proto-Oncogene Proteins c-jun / immunology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D1 / metabolism
  • Rotation
  • Transcription Factors / analysis
  • Transcription Factors / biosynthesis
  • Transcription Factors / immunology

Substances

  • Antibodies
  • DNA-Binding Proteins
  • Dopamine Uptake Inhibitors
  • Early Growth Response Protein 1
  • Egr1 protein, rat
  • Immediate-Early Proteins
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-jun
  • Receptors, Dopamine D1
  • Transcription Factors
  • Cocaine
  • Dextroamphetamine
  • Dopamine