Localization of striatal opioid gene expression, and its modulation by the mesostriatal dopamine pathway: an in situ hybridization study.

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.