kappa-opioid regulation of neuronal activity in the rat supraoptic nucleus in vivo.
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.
Brown
C H
CH
Department of Physiology, University Medical School, Edinburgh EH8 9AG, United Kingdom.
Ludwig
M
M
Leng
G
G
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D003712:Dendrites / Q000737:chemistry / Q000502:physiology; D015536:Down-Regulation / Q000187:drug effects; D004399:Dynorphins / Q000494:pharmacology; D004594:Electrophysiology; D005260:Female; D007275:Injections, Intravenous; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D017551:Microdialysis; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000737:chemistry* / Q000502:physiology / Q000648:ultrastructure; D010121:Oxytocin / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D013495:Supraoptic Nucleus / Q000166:cytology*; D014667:Vasopressins / Q000502:physiology
D018712:Analgesics, Non-Narcotic; D009292:Narcotic Antagonists; D017473:Receptors, Opioid, kappa; D014667:Vasopressins; D009270:Naloxone; C051844:norbinaltorphimine; D010121:Oxytocin; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D004399:Dynorphins