Chronic Neuroleptic Administration Reduces Striatal Substance P mRNA and the Localization of Substance P mRNA in Rat Brain by In Situ Hybridization

Chronic treatment of rats with the neuroleptic drug haloperidol, a dopamine receptor antagonist, decreases the concentration of substance P (SP) in the substantia nigra (SN). This drug-induced reduction in peptide concentration was found to be concomitant with the reduction of the mRNA in the striatum which encodes SP. The mRNA encoding substance K (SK), a related tachykinin peptide, was similarly reduced by haloperidol, whereas striatal enkephalin-mRNA was elevated. The results demonstrate that pharmacological blockade of dopamine receptors can differentially affect neuropeptide gene expression.SP-mRNA was localized by in situ hybridization. Brain structures that gave positive hybridization signals were caudate, premammillary area and arcuate nucleus of the hypothalamus, central nucleus of the amygdala, nucleus accumbens, and medial habenula.