Effects of the isomers of N-n-propylnorapomorphine and haloperidol on regional concentrations of neurotensin in rat brain

Charles Nemeroff, Clinton D. Kilts, Beth Levant, Garth Bissette, Alexander Campbell, Ross J. Baldessarini

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Rats were treated for 10 days with haloperidol (0.2 or 3 mg/kg/day intraperitoneally [IP]), with either S(+) or R(-) N-n-propylnorapomorphine (NPA; 3 mg/kg IP three times daily) or saline as a placebo control. Brain was microdissected into 11 regions for radioimmunoassay of neurotensin (NT)-like activity under coded ("blind") conditions. Concentrations of NT in rat brain regions ranked central amygdaloid nucleus > ventral bed nucleus > ventral tegmentum > dorsal bed nucleus > arcuate nucleus > substantia nigra > nucleus accumbens septi (accumbens) > piriform cortex > nucleus caudatus (caudate) > mesoprefrontal cortex > cingulate cortex, similar to previous observations. Since untreated and placebo-injected control results were indistinguishable, a stress artifact is unlikely to account for the findings. Haloperidol at the lower dose produced no significant changes but, at the higher dose, yielded relatively large (42%-143%) increases of NT concentrations in accumbens, caudate, and substantia nigra. S(+)NPA, which has some properties as a limbic-selective dopamine antagonist, yielded smaller (55%-66%) but significant average increases of NT in accumbens and piriform cortex, and lesser trends toward increases (40%-51%) in caudate, nigra, and mesoprefrontal cortex - all persisting for 5 days after treatment, whereas the R(-) enantiomer, a potent dopaminergic agonist, increased NT only in nigra (by 112%). These observations confirm previous results with haloperidol and add to the impression that S(+)-NPA shares some properties of atypical antipsychotic agents.

Original languageEnglish
Pages (from-to)27-33
Number of pages7
JournalNeuropsychopharmacology
Volume4
Issue number1
StatePublished - Jan 1 1991
Externally publishedYes

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Keywords

  • Aporphines
  • Haloperidol
  • Limbic system
  • N-n-propylnorapomorphine
  • Neurotensin

ASJC Scopus subject areas

  • Pharmacology

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