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Coordinate expression of c-fos and jun B is induced in the rat striatum by cocaine
R Moratalla1, E A Vickers, H A Robertson
1Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge 02139.
Abstract:
In cells in culture, specific stimuli induce selective patterns of immediate-early gene induction. In the present study, we tested for such selectivity of stimulated gene expression by monitoring the expression of fos/jun gene mRNAs in the striatum in rats treated in vivo with the indirect dopamine agonist cocaine. We found by Northern blot and in situ hybridization analysis that cocaine induces the coordinate expression of c-fos and jun B mRNAs in neurons of the rat's striatum. By contrast, another immediate-early gene of the leucine-zipper family, c-jun, was not induced in striatal neurons by cocaine at any time tested from 1 to 24 hr after treatment. With the same probe, we could detect the induction of c-jun mRNA (as well as that of c-fos and jun B mRNAs) in the hippocampus following administration of pentylenetetrazol. The induction of expression of c-fos and jun B was rapid and transient, with peak expression occurring at approximately 1 hr after cocaine administration, and the induction of the two genes was in similar striatal sites. These results establish that differential patterns of expression of fos/jun genes occur in striatal neurons following exposure to cocaine, a potent psychomotor stimulant. We suggest that these tissue-specific patterns of gene expression may contribute to the response specificity of striatal neurons to stimulation by monoamines including dopamine.
Insights
Cocaine selectively induces c-fos and jun B gene expression in rat striatum neurons, but not c-jun. This differential gene response may explain how neurons react to dopamine stimulation.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Immediate-early genes (IEGs) like fos/jun are rapidly activated by cellular stimuli.
- Understanding IEG induction patterns is crucial for deciphering neuronal responses to drugs and neurotransmitters.
Purpose of the Study:
- To investigate the selectivity of IEG induction in rat striatum neurons following cocaine administration.
- To compare the expression patterns of c-fos, c-jun, and jun B mRNAs in response to cocaine.
Main Methods:
- In vivo administration of cocaine to rats.
- Northern blot analysis to detect mRNA levels.
- In situ hybridization to visualize gene expression in specific brain regions.
Main Results:
- Cocaine induced coordinate expression of c-fos and jun B mRNAs in striatal neurons.
- c-jun mRNA was not induced in striatal neurons by cocaine.
- Differential induction of fos/jun genes was observed, with c-fos and jun B peaking at 1 hour post-treatment.
- Pentylenetetrazol induced c-jun, c-fos, and jun B mRNAs in the hippocampus.
Conclusions:
- Cocaine exposure leads to differential expression patterns of fos/jun genes in the rat striatum.
- These specific gene expression patterns may underlie the distinct neuronal responses to monoaminergic stimulation, including dopamine.