Regional distribution and regulation of preprosomatostatin messenger RNA in the striatum, as revealed by in situ hybridization histochemistry

Abstract

Quantitative in situ hybridization was used to examine the regional distribution of preprosomatostatin messenger RNA (PPSOM mRNA) in the dorsal striatum (caudo-putamen) of the mouse. In addition, because mesencephalic dopaminergic neurons project to the striatum where they play a role in the regulation of peptide-containing neurons, the effect of dopamine receptor blockade on the levels of striatal PPSOM mRNA was determined. Sagittal brain sections from male Swiss Webster mice were processed for in situ hybridization histochemistry using an 35S-radiolabelled RNA probe in order to quantify levels of PPSOM mRNA in individual neurons of the dorsal caudo-putamen using light microscopy and computer-assisted grain analysis. In control animals, individual neurons of the dorsolateral caudo-putamen had higher levels of PPSOM mRNA than did those of the medial part of the structure. Treated mice were injected with fluphenazine- N-mustard (FNM), an antagonist which, at the dose used (4 μmol/kg), irreversibly blocks dopamine D 2 but not D 1 receptors in the mouse striatum. FNM treatment (for 2 days, twice a day) produced an increase in striatal dopamine turnover and a decrease in PPSOM mRNA levels in the lateral, but not the medial striatum. The results indicate that there is a lateral to medial gradient in the levels of PPSOM mRNA per individual neuron in the dorsal caudo-putamen of control animals, which is abolished by FNM treatment. This suggests that intrinsic striatal somatostatinergic neurons are differentially regulated by dopamine, depending on their lateromedial location within the striatum.