kappa-opioid regulation of neuronal activity in the rat supraoptic nucleus in vivo

C H Brown, M Ludwig, G Leng

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

We investigated the influence of endogenous kappa-opioids on the activity of supraoptic neurons in vivo. Administration of the kappa-antagonist nor-binaltorphimine (200 micrograms/kg, i.v.), increased the activity of phasic (vasopressin), but not continuously active (oxytocin), supraoptic neurons by increasing burst duration (by 69 +/- 24%) and decreasing the interburst interval (by 19 +/- 11%). Similarly, retrodialysis of nor-binaltorphimine onto the supraoptic nucleus increased the burst duration (119 +/- 57% increase) of vasopressin cells but did not alter the firing rate of oxytocin cells (4 +/- 8% decrease). Thus, an endogenous kappa-agonist modulates vasopressin cell activity by an action within the supraoptic nucleus. To eliminate kappa-agonist actions within the supraoptic nucleus, we infused the kappa-agonist U50,488H (2.5 micrograms/hr at 0.5 micrograms/hr) into one supraoptic nucleus over 5 d to locally downregulate kappa-receptor function. Such infusions reduced the spontaneous activity of vasopressin but not oxytocin cells and reduced the proportion of cells displaying spontaneous phasic activity from 26% in vehicle-infused nuclei to 3% in U50, 488H-infused nuclei; this treatment also prevented acute inhibition of both vasopressin and oxytocin cells by U50,488H (1000 micrograms/kg, i.v.), confirming functional kappa-receptor downregulation. In U50, 488H-infused supraoptic nuclei, vasopressin cell firing rate was increased by nor-binaltorphimine (100 and 200 micrograms/kg, i.v.) but not to beyond that found in vehicle-treated nuclei, indicating that these cells were not U50,488H-dependent. Thus, normally functioning kappa-opioid mechanisms on vasopressin cells are essential for the expression of phasic firing.

Original languageEnglish
Pages (from-to)9480-8
Number of pages9
JournalJournal of Neuroscience
Volume18
Issue number22
Publication statusPublished - 15 Nov 1998

Keywords / Materials (for Non-textual outputs)

  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
  • Analgesics, Non-Narcotic
  • Animals
  • Cells, Cultured
  • Dendrites
  • Down-Regulation
  • Dynorphins
  • Electrophysiology
  • Female
  • Injections, Intravenous
  • Membrane Potentials
  • Microdialysis
  • Naloxone
  • Naltrexone
  • Narcotic Antagonists
  • Neurons
  • Oxytocin
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Opioid, kappa
  • Supraoptic Nucleus
  • Vasopressins

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