Neuroleptic drug treatment alters in vitro central neurotensin metabolism

Thomas P. Davis, Alison Culling-Berglund

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Neurotensin (NT) has been shown to possess pharmacological properties associated with neuroleptic drugs. To determine if chronic haloperidol (HL; 3.5 mg/kg/day) or chlorpromazine (CPZ; 4.2 mg/kg/day) treatment affects central NT metabolism, HL and CPZ were perfused via Alzet® minipumps into male Sprague-Dawley rats for 8 days. Purified synaptosomal plasma membranes (pSPM) were isolated and time-course incubated with NT (100 μM; 30-120 min). All samples were analyzed by high resolution, reversed-phase high performance liquid chromatography. HL and CPZ caused an increase in NT metabolism at the pSPM. Although an increase in NT metabolism would result in a loss of biological activity, it does lead to a significant accumulation of the biologically active NT fragment NT-(9-13), which has been shown to bind to the NT receptor. Therefore, neuroleptic drug treatment alters NT metabolism at the pSPM, leading to the formation of a fragment with antinociceptive activity.

Original languageEnglish (US)
Pages (from-to)253-260
Number of pages8
JournalPsychoneuroendocrinology
Volume12
Issue number4
DOIs
StatePublished - 1987

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ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Psychiatry and Mental health
  • Biological Psychiatry

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