This study examined the influence of 5-hydroxytryptamine (5HT) on the biosynthesis of striatal dynorphin and substance P systems in Sprague-Dawley rats. The 5HT uptake inhibitor, fluoxetine was used as a pharmacological tool to enhance the serotonergic function by a repeated administration regimen (15 or 30 mg/kg/day for four days). The levels of peptides (dynorphin A 1-8, DYN; substance P, SP) were determined by radioimmunoassays. The mRNAs coding for the peptide precursors, prodynorphin (PD) and preprotachykinin (PPT) were quantified by Northern blot analyses. In addition, the levels of amines and metabolites were determined by HPLC. Repeated administration of the higher dosage regimen increased SP and DYN levels; the increased peptide levels were associated with increased abundance of PD and PPT mRNA. A single dose of 30 mg/kg fluoxetine did not affect the peptide systems studied. The results suggest that a sustained augmentation of serotonergic function positively regulates striatal gene expression of dynorphin and tachykinin neurons resulting in increased peptide biosynthesis.
|Original language||English (US)|
|Number of pages||7|
|Journal||Neuroscience Research Communications|
|State||Published - Jan 1 1995|
- Substance P
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