Effects of 5 daily injections of the neurotensin-mimetic NT69L on the expression of neurotensin receptors in rat brain

Rui Wang, Mona Boules, Elisa Gollatz, Katrina Williams, William Tiner, Elliott Richelson

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

The effects of one or five daily intraperitoneal injections of a neurotensin (NT) receptor agonist NT69L (2 mg/kg, i.p.) on the expression of NT (NTS), dopamine 1 and 2 receptors, tyrosine hydroxylase, and DOPA decarboxylase using immunohistochemical and real-time PCR were investigated in rats. Except for the striatum, acute injection of NT69L did not affect neurotensin receptors as compared to saline control. However, 5 daily injections of NT69L resulted in down-regulation of both NTS-1 protein and mRNA levels in several brain regions with the striatum showing a dramatic decrease in NTS-1 expression (P < 0.05). The down-regulation of NTS-1 in the striatum, hypothalamus, and substania nigra (SN) after 5 daily injections was confirmed by autoradiography. Acute injection of NT69L increased NTS-2 mRNA and protein level in prefrontal cortex (PFC). NTS-3 mRNA expression and protein levels were slightly down-regulated in hypothalamus, periaqueductal gray (PAG), and SN, though the difference was not significant. The results indicated a difference in the profile of NT receptors expression in response to NT69L. Tyrosine hydroxylase (TH) and DOPA decarboxylase (DDC) mRNA was significantly down-regulated in striatum but not in SN. Interestingly, Nurr1, a transcriptional activator of TH, was dramatically up-regulated in striatum, but down-regulated in PFC, suggesting that different modulating mechanisms may participate in NT69L tolerance in different regions. The present results suggest that distinct NT receptors involved in the effects exerted by NT69L may contribute to the interactions of NT69L with both neural networks and cellular proteins.

Original languageEnglish (US)
Pages (from-to)24-34
Number of pages11
JournalMolecular Brain Research
Volume138
Issue number1
DOIs
StatePublished - Jul 29 2005

Keywords

  • Neurotensin agonist
  • Neurotensin receptors
  • Rat
  • Tolerance
  • Tyrosine hydroxylase
  • mRNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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