Abstract

Adaptive changes in brain neurotensin (NT) receptors were investigated in rats after repeated administration of SR 48692, a potent and selective non-peptide NT receptor antagonist. Administration of SR 48692 (1 mg/kg i.p.) for 15 days did not alter NT content in the brain but highly enhanced the expression of NT receptor mRNA as shown by quantitative in situ hybridization. The increase of the signal was observed in numerous areas of the brain, such as the anterior cingulate, perirhinal and retrosplenial cortices, the suprachiasmatic nucleus, the ventral tegmental area, the substantia nigra and the posterior cortical nucleus of the amygdaloid complex. Moreover, the SR 48692 treatment induced the expression of NT receptor mRNA in several nuclei of the diencephalon where it could not be detected in basal conditions. Immunoblot analysis with a specific antibody directed against the rat cloned NT receptor revealed an important increase in NT receptor protein in the brain of SR 48692-treated rats, correlating well with the increase in NT receptor mRNA levels. Surprisingly, the number and the affinity constant of NT binding sites determined on brain membrane homogenates remained unchanged after SR 48692 treatment, even after membrane permeabilization with low concentrations of digitonin. These results suggest that chronic treatment with a specific NT antagonist induces an up-regulation of NT receptors at the level of mRNA and protein. Moreover, they indicate that after a chronic treatment with SR 48692, the number of NT binding sites remains stable in contrast to what is observed after 5-day treatment or with central monoaminergic receptor following their long-term blockade.

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.