Effects of amphetamine and cocaine treatment on c-Fos, Jun-B, and Krox-24 expression in rats with intrastriatal dopaminergic grafts.
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.
Rodriguez
J J
JJ
INSERM U.259, Domaine de Carreire, Rue Camille Saint Saëns, Bordeaux Cedex, 33077, France.
Montaron
M F
MF
Aurousseau
C
C
Le Moal
M
M
Abrous
D N
DN
D000818:Animals; D000906:Antibodies; D001522:Behavior, Animal / Q000187:drug effects; D016380:Brain Tissue Transplantation; D003042:Cocaine / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000276:immunology; D003913:Dextroamphetamine / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D051766:Early Growth Response Protein 1; D016332:Fetal Tissue Transplantation; D006085:Graft Survival; D017874:Immediate-Early Proteins; D008297:Male; D017072:Neostriatum / Q000601:surgery; D009474:Neurons / Q000737:chemistry / Q000378:metabolism / Q000637:transplantation*; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology; D016755:Proto-Oncogene Proteins c-jun / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D012399:Rotation; D014157:Transcription Factors / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology
D000906:Antibodies; D004268:DNA-Binding Proteins; D018765:Dopamine Uptake Inhibitors; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D017447:Receptors, Dopamine D1; D014157:Transcription Factors; D003042:Cocaine; D003913:Dextroamphetamine; D004298:Dopamine