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Title: Opiate actions on central and systemic oxytocin release
Author: Coombes, Julia E.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1991
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The experiments in this thesis were designed to investigate the modification of oxytocin secretion by mechanisms acting at the posterior pituitary gland and on centrally-projecting oxytocin neurones. Electrical stimulation of the neurohypophysial stalk to release oxytocin combined with autobioassay of oxytocin secretion was used in anaesthetized, lactating rats to compare actions of opioid-receptor subtype specific agonists of oxytocin neurone terminals in the posterior pituitary. The kappa-receptor was identified as the opioid-receptor subtype responsible for inhibition of oxytocin secretion at the posterior pituitary by the use of the selective opioid-receptor agonists U50,488H and morphine. It was determined that in rats with oxytocin neurones made tolerant to morphine there was no cross tolerance to the actions of kappa-opioid agonists at the posterior pituitary. Electrically-stimulated isolated posterior pituitaries in vitro were used to study effects on oxytocin of opioid-antagonists with different receptor affinities: the non-selective agonist naloxone was more effective than the relative μ-selective RX8008M and MR2266. Cerebrospinal-fluid (CSF) samples were collected from the cisterna magna, for oxytocin radioimmunoassay from anaesthetized rats, which were also blood sampled to monitor opioid actions on centrally projecting oxytocin neurones. It was found that oxytocin neurones projecting centrally and to the posterior pituitary could not be made dependent upon the kappa-agonist U50,488H, as assessed by lack of withdrawal excitation of oxytocin secretion after naloxone. Dependence upon the μ-opioidreceptor, morphine, could be achieved for oxytocin neurones releasing into CSF as well as ocytocin neurones secreting into blood; it was concluded that both centrally-releasingand magnocellular neurones can be inhibited by opioids. Studies on morphine-dependent rats with ablated paraventricular nuclei, indicated that magnocellular supraoptic neurones could release oxytocin into CSF during morphine withdrawal.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available