Related Experiment Videos
Localization of striatal opioid gene expression, and its modulation by the mesostriatal dopamine pathway: an in situ
1Abt. Neuropharmakologie, Max-Planck-Institut für Psychiatrie, Martinsried, F.R.G.
Abstract:
In situ hybridization was used to study the macroscopic distribution and regulatory control of proenkephalin mRNA and prodynorphin mRNA in rat striatum. While proenkephalin mRNA was widely distributed throughout the striatum, levels of prodynorphin mRNA were highest in the medial and ventral portions of the striatum. Furthermore, in contrast to the results for proenkephalin mRNA, the levels of prodynorphin mRNA appeared higher in the nucleus accumbens than in the striatum. The mesostriatal dopaminergic pathway was destroyed by discrete, unilateral injection of 6-hydroxy-dopamine (6-OHDA) into either the substantia nigra or the neighboring ventral tegmental area (VTA). Lesions of the substantia nigra caused a dramatic ipsilateral increase in the hybridization signal for proenkephalin mRNA, but no change was observed in the hybridization signal for prodynorphin mRNA. Similar effects were seen with VTA lesions. Since destruction of the mesostriatal dopamine system elevates the levels of proenkephalin mRNA, but not of prodynorphin mRNA, in the striatal target neurons, it appears that the mesostriatal pathway exerts a tonic and selective suppression of striatal proenkephalin gene expression at the mRNA level.
Insights
The mesostriatal dopamine pathway selectively suppresses proenkephalin mRNA levels in the rat striatum. Destroying this pathway increases proenkephalin mRNA but not prodynorphin mRNA.
Area of Science:
- Neuroscience
- Molecular Biology
Background:
- Proenkephalin (PENK) and prodynorphin (PDYN) are key opioid peptides in the striatum.
- The mesostriatal dopaminergic pathway's role in regulating PENK and PDYN gene expression is not fully understood.
Purpose of the Study:
- To investigate the distribution and regulation of proenkephalin mRNA and prodynorphin mRNA in the rat striatum.
- To determine the effect of mesostriatal dopaminergic pathway lesions on these mRNA levels.
Main Methods:
- In situ hybridization was employed to visualize and quantify proenkephalin mRNA and prodynorphin mRNA.
- Discrete, unilateral lesions of the substantia nigra or ventral tegmental area (VTA) were induced using 6-hydroxy-dopamine (6-OHDA).
Main Results:
- Proenkephalin mRNA was widely distributed in the striatum, while prodynorphin mRNA was concentrated in medial and ventral regions.
- Lesions of the dopaminergic pathway significantly increased ipsilateral proenkephalin mRNA levels.
- Prodynorphin mRNA levels remained unchanged following dopaminergic pathway lesions.
Conclusions:
- The mesostriatal dopaminergic pathway exerts tonic, selective suppression of proenkephalin gene expression at the mRNA level in the striatum.
- This pathway does not appear to regulate prodynorphin gene expression in the same manner.