Blunting of the neurotensin mRNA response to haloperidol in the striatum of aging rats: possible relationship to decline in dopamine D2 receptor expression

Dorcas J. Dobie, Kalpana M. Merchant, Mark W. Hamblin, Govind T. Vatassery, Maurice W. Dysken, Daniel M. Dorsa

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Neuroleptic drugs such as haloperidol (H) induce a rapid increase in neurotensin/neuromedin N (NT/N) gene expression in the dorsolateral striatum (DLSt) and nucleus accumbens (NA) in young adult rats. This effect may be mediated by post-receptor effectors that are activated by dopamine D2 receptor antagonism. The regional pattern of induction of neurotensin gene expression correlates with the side effect profile of particular neuroleptics. As motor side effects of H differ in aged animals, we hypothesized that the regional expression of the neurotensin gene may differ between young and old animals. We administered H or saline acutely to 3, 14, and 25 month-old Fischer 344 rats, followed by in situ hybridization and quantitative autradiography for NT/N mRNA. There was a significant age effect on the H-induced NT/N mRNA response in the DLSt, but not the NA, of older animals. In addition to the blunted NT/N mRNA response, significant decreases in D2 receptor mRNA were observed in the lateral striatum of another group of young, middle-aged, and aged rats. Age-related blunting of the NT/N mRNA response to H in the DLSt may be due in part to a decrease in D2 receptors in this structure.

Original languageEnglish (US)
Pages (from-to)105-113
Number of pages9
JournalBrain research
Volume616
Issue number1-2
DOIs
StatePublished - Jul 9 1993

Keywords

  • Aging
  • Dopamine receptor
  • Fischer 344
  • Haloperidol
  • In situ hybridization
  • Neurotensin
  • Nucleus accumbens
  • Striatum

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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