Central administration of orexin A suppresses basal and domperidone stimulated plasma prolactin

S. H. Russell, M. S. Kim, C. J. Small, C. R. Abbott, D. G.A. Morgan, Shahrad Taheri, K. G. Murphy, J. F. Todd, M. A. Ghatei, S. R. Bloom

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Abstract

Orexin immunoreactive fibres are abundant in the hypothalamus suggesting a neuroendocrine regulatory role. Intracerebroventricular (ICV) administration of orexin A suppressed plasma prolactin in male rats by 71% at 20 min post-injection and 83% at 90 min post-injection (P <0.005 vs saline at both time points). To investigate whether this effect was through the tuberoinfundibular dopaminergic (TIDA) system, a supra-maximal dose of domperidone, a dopamine receptor antagonist, was injected intraperitoneally (i.p.) prior to ICV injection of orexin A. ICV orexin A significantly suppressed domperidone (9 mg/kg)-stimulated plasma prolactin levels, by up to 40% (i.p. domperidone + ICV orexin A 3 nmol 34.5 ±7.4 ng/ml and i.p. domperidone + ICV orexin A 20 nmol 43.5 ±4.3 ng/ml, both P <0.005 vs i.p. domperidone + ICV saline 57.9 ± 2.7 ng/ml). Orexin A, 100 nM, significantly stimulated release of neurotensin, vasoactive intestinal polypeptide, somatostatin, corticotropin releasing factor and luteinizing hormone releasing hormone, but had no effect on release of dopamine, thyrotropin releasing hormone (TRH), vasopressin or melanin-concentrating hormone from hypothalamic explants in vitro. Orexin A did not alter basal or TRH stimulated prolactin release in dispersed pituitary cells harvested from male rats. The data suggest that ICV administration of orexin A suppresses plasma prolactin in part through a pathway independent of the dopaminergic system.

Original languageEnglish
Pages (from-to)1213-1218
Number of pages6
JournalJournal of Neuroendocrinology
Volume12
Issue number12
DOIs
Publication statusPublished - 2000
Externally publishedYes

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Keywords

  • Domperidone
  • Hypocretin
  • Intracerebroventricular
  • Orexin
  • Prolactin

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

Cite this

Russell, S. H., Kim, M. S., Small, C. J., Abbott, C. R., Morgan, D. G. A., Taheri, S., Murphy, K. G., Todd, J. F., Ghatei, M. A., & Bloom, S. R. (2000). Central administration of orexin A suppresses basal and domperidone stimulated plasma prolactin. Journal of Neuroendocrinology, 12(12), 1213-1218. https://doi.org/10.1046/j.1365-2826.2000.00582.x