Differential induction of neurotensin and c-fos gene expression by typical versus atypical antipsychotics

Kalpana M. Merchant, Daniel M. Dorsa

Research output: Contribution to journalArticle

166 Scopus citations

Abstract

Precise neural mechanisms underlying the pathophysiology and pharmacotherapy of psychotic disorders remain largely unknown. Present studies investigated the effects of various antipsychotic drugs on expression of the gene encoding the purported endogenous antipsychotic-like peptide neurotensin (NT) in striatal regions of the rat brain. The results demonstrate that several clinically efficacious antipsychotic drugs selectively and specifically increase expression of NT/neuromedin N (NT/N) mRNA in the shell of the nucleus accumbens, a region of the forebrain associated with limbic systems. On the other hand, only typical antipsychotics that cause a high incidence of acute motor side effects increased the expression of NT/N mRNA in the dorsolateral striatum, an extrapyramidal region primarily involved in motor control. In addition, it appears that distinct mechanisms may be involved in the effects of antipsychotics on NT/N gene expression in the dorsolateral striatum versus the accumbal shell. Thus neuroleptic-induced increases in NT/N mRNA expression in the dorsolateral striatum were preceded by a rapid and transient activation of c-fos mRNA, whereas none of the antipsychotics affected c-fos mRNA expression in the accumbal shell. The anatomical characteristics of NT/N gene expression induced by typical versus atypical antipsychotics raise the possibility that increased activity of specific NT neurons may contribute to the therapeutic effects (NT neurons in the accumbal shell) or motor side effects (NT neurons in the dorsolateral striatum) of these drugs.

Original languageEnglish (US)
Pages (from-to)3447-3451
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume90
Issue number8
DOIs
StatePublished - Apr 15 1993

Keywords

  • Caudate-putamen
  • Extrapyramidal side effects
  • Nucleus accumbens shell
  • mRNA

ASJC Scopus subject areas

  • General

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