Regulation of the neurotensin NT(1) receptor in the developing rat brain following chronic treatment with the antagonist SR 48692.

The aim of the present study was to investigate the role of neurotensin in the regulation of NT(1) receptors during postnatal development in the rat brain. Characterization of the ontogeny of neurotensin concentration and [(125)I]neurotensin binding to NT(1) receptors in the brain at different embryonic and postnatal stages showed that neurotensin was highly expressed at birth, reaching peak levels at postnatal day 5 (P5) and decreasing thereafter. The transient rise in neurotensin levels preceded the maximal expression of NT(1) receptors, observed at P10, suggesting that neurotensin may influence the developmental profile of NT(1) receptors. Using primary cultures of cerebral cortex neurons from fetal rats, we showed that exposure to the neurotensin agonist JMV 449 (1 nM) decreased (-43%) the amount of NT(1) receptor mRNA measured by reverse transcription-PCR, an effect that was abolished by the nonpeptide NT(1) receptor antagonist SR 48692 (1 microM). However, daily injection of SR 48692 to rat pups from birth for 5, 9, or 15 days did not modify [(125)I]neurotensin binding in brain membrane homogenates. Moreover, postnatal blockade of neurotensin transmission did not alter the density and distribution of NT(1) receptors assessed by quantitative autoradiography nor NT(1) receptor mRNA expression measured by in situ hybridization in the cerebral cortex, caudate-putamen, and midbrain. These results suggest that although NT(1) receptor expression can be regulated in vitro by the agonist at an early developmental stage, neurotensin is not a major factor in the establishment of the ontogenetic pattern of NT receptors in the rat brain.