Sensitivity of magnocellular oxytocin neurones to opioid antagonists in rats treated chronically with intracerebroventricular (i.c.v.) morphine.
The identity of the subtype of opioid receptor mediating morphine dependence in relation to oxytocin neurones was investigated. Virgin female rats were implanted with a subcutaneous osmotic minipump to infuse morphine continuously (up to 50 micrograms/h) into a lateral cerebral ventricle. After 5 days of morphine infusion, rats were anesthetized with urethane, and the electrical activity of electrophysiologically identified supraoptic neurones was recorded extracellularly while opioid antagonists were injected i.v. Putative oxytocin cells were excited following low doses of naloxone HCl: 4/7 cells were excited by 1 microgram/kg, 6/7 cells by 2.5 micrograms/kg, and 11/13 cells by doses of 5-50 micrograms/kg. MR2266 ((-)-5,9 alpha-diethyl-2-(3-furylmethyl)-2'-hydroxy-6,7-benzomorphan: an antagonist with much greater affinity for kappa-subtype opioid receptors than naloxone) excited oxytocin cells less potently: none of 9 cells was excited by 10 micrograms/kg MR2266, 2/4 cells were by 25-50 micrograms/kg, 3/9 cells by 100 micrograms/kg and only 4/8 by 200-500 micrograms/kg. At low concentrations naloxone is selective for mu-subtype opioid receptors, hence the morphine dependence of oxytocin neurones is probably via mu-receptors. Naloxone methylbromide (MRZ), a quaternary ammonium derivative of naloxone, excited oxytocin cells in morphine-treated rats, but was at least 10 times less potent than naloxone. Thus part of the morphine-withdrawal excitation of oxytocin neurones may be mediated by mu-receptors outside the blood-brain barrier.
Leng
G
G
AFRC Institute of Animal Physiology and Genetics Research, Babraham, Cambridge, U.K.
Russell
J A
JA
Grossmann
R
R
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001575:Benzomorphans / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007276:Injections, Intraventricular; D009019:Morphinans / Q000494:pharmacology*; D009020:Morphine / Q000008:administration & dosage*; D009270:Naloxone / Q000494:pharmacology*; D010121:Oxytocin / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D014726:Vestibular Nuclei / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D001575:Benzomorphans; D009019:Morphinans; D009270:Naloxone; D010121:Oxytocin; C027247:MR 2266; D009020:Morphine