Rapid estradiol-17beta modulation of opioid actions on the electrical and secretory activity of rat oxytocin neurons in vivo.
During pregnancy, emergence of endogenous opioid inhibition of oxytocin neurons is revealed by increased oxytocin secretion after administration of the opioid receptor antagonist, naloxone. Here we show that prolonged estradiol-17beta and progesterone treatment (mimicking pregnancy levels) potentiates naloxone-induced oxytocin secretion in urethane-anesthetized virgin female rats. We further show that estradiol-17beta alone rapidly modifies opioid interactions with oxytocin neurons, by recording their firing rate in anesthetized rats sensitized to naloxone by morphine dependence. Naloxone-induced morphine withdrawal strongly increased the firing rate of oxytocin neurons in morphine dependent rats. Estradiol-17beta did not alter basal oxytocin neuron firing rate over 30 min, but amplified naloxone-induced increases in firing rate. Firing pattern analysis indicated that acute estradiol-17beta increased oxytocin secretion in dependent rats by increasing action potential clustering without an overall increase in firing rate. Hence, rapid estradiol-17beta actions might underpin enhanced oxytocin neuron responses to naloxone in pregnancy.
Brown
Colin H
CH
Centre for Neuroendocrinology and Department of Physiology, Otago School of Medical Sciences, University of Otago, P.O. Box 913, Dunedin, 9054, New Zealand. colin.brown@stonebow.otago.ac.nz
Brunton
Paula J
PJ
Russell
John A
JA
D000200:Action Potentials / Q000187:drug effects; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D004594:Electrophysiology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D009021:Morphine Dependence / Q000503:physiopathology / Q000523:psychology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010121:Oxytocin / Q000097:blood / Q000502:physiology*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; D009270:Naloxone; D004958:Estradiol; D010121:Oxytocin