Regulation of striatal prodynorphin mRNA levels by the raphe-striatal pathway

Peptides derived from proenkephalin and prodynorphin are known to be located in striatal projection neurones. Anatomical studies have shown the presence of a major serotonergic projection from the dorsal raphe nucleus to the striatum, although the function of this pathway is unknown. We have used in situ nucleic acid hybridization to investigate a possible role of this serotonergic innervation in the regulation of striatal opioid gene expression. The levels of proenkephalin mRNA and prodynorphin mRNA were determined in rat striatum and nucleus accumbens. Destruction of the dorsal raphe nucleus by microinjection of 5,7-dihydroxytryptamine failed to affect the levels of proenkephalin mRNA in any region. However, the levels of prodynorphin mRNA were significantly reduced in the medial nucleus accumbens and caudomedial striatum. This implies that activity in the raphe-striatal serotonin pathway mediates a tonic and selective enhancement of prodynorphin gene expression in the striatal target cells. This is in contrast to the tonic suppression of proenkephalin gene expression mediated by the mesostriatal dopamine pathway.