Regulation of the neurotensin NT1 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 NT1 receptors during postnatal development in the rat bra in. Characterization of the ontogeny of neurotensin concentration and [I-12 5]neurotensin binding to NT1 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. Th e transient rise in neurotensin levels preceded the maximal expression of N T1 receptors, observed at P10, suggesting that neurotensin may influence th e developmental profile of NT1 receptors. Using primary cultures of cerebra l cortex neurons from fetal rats, we showed that exposure to the neurotensi n agonist JMV 449 (1 nM) decreased (-43%) the amount of NT1 receptor mRNA m easured by reverse transcription-PCR, an effect that was abolished by the n onpeptide NT1 receptor antagonist SR 48692 (1 mu M). However, daily injecti on of SR 48692 to rat pups from birth for 5, 9, or 15 days did not modify [ I-125]neurotensin binding in brain membrane homogenates. Moreover, postnata l blockade of neurotensin transmission did not alter the density and distri bution of NT1 receptors assessed by quantitative autoradiography nor NT1 re ceptor mRNA expression measured by in situ hybridization in the cerebral co rtex, caudateputamen, and midbrain. These results suggest that although NT1 receptor expression can be regulated in vitro by the agonist at an early d evelopmental stage, neurotensin is not a major factor in the establishment of the ontogenetic pattern of NT receptors in the rat brain. (C) 2000 Wiley -Liss, Inc.