Effects of amphetamine and cocaine treatment on c-Fos, Jun-B, and Krox-24 expression in rats with intrastriatal dopaminergic grafts.
Experimental Neurology. 1999-09-01; 159(1): 139-152
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1. Exp Neurol. 1999 Sep;159(1):139-52.
Effects of amphetamine and cocaine treatment on c-Fos, Jun-B, and Krox-24
expression in rats with intrastriatal dopaminergic grafts.
Rodriguez JJ(1), Montaron MF, Aurousseau C, Le Moal M, Abrous DN.
(1)INSERM U.259, Domaine de Carreire, Rue Camille Saint Saëns, Bordeaux Cedex,
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.
Copyright 1999 Academic Press.
PMID: 10486183 [Indexed for MEDLINE]