CHRONIC NONPEPTIDE NEUROKININ RECEPTOR ANTAGONIST TREATMENT ALTERS STRIATAL TACHYKININ PEPTIDE AND RECEPTOR GENE-EXPRESSION IN THE RAT

The neurokinin-l receptor (NK-1R) and the tachykinin peptide substance P (SP) are found throughout the central nervous system (CNS) and are involved in the regulation of sensory, cardiovascular, and inflammator y function. Selective antagonists for the NK-1R such as CP-122,721 blo ck NK-1R-mediated responses both in vitro and in vivo. This study inve stigated the effects of long-term daily CP-122,721 treatment on gene e xpression of SP and the NK-1R in the striatum and hindbrain of the rat . The striatum and hindbrain of rats receiving CP122,721 (5, 30, or 15 0 mg/kg) once-daily for 30 days were assayed for SP- and NK-1R-encodin g mRNAs using solution hybridization-nuclease protection assays. Resul ts show that treatment with CP-122,721 significantly increased SP-enco ding mRNA and NK-1R mRNA levels in the striatum, but not in the hindbr ain. The ability of CP122,721 to alter SP and NK-1R gene expression ma y provide a use for non-peptide neurokinin receptor antagonists in the modulation of systems regulated by NK-1R function. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.