Suppressed oxytocin neuron responses to immune challenge in late pregnant rats: a role for endogenous opioids.
Cytokine challenge (mimicking infection) with systemic interleukin-1beta (IL-1beta) stimulates oxytocin neurons via a noradrenergic brainstem pathway similar to that involved in parturition. As the responses of oxytocin neurons to several stimuli are reduced in late pregnancy, we have investigated whether responses to IL-1beta are also suppressed. In virgin Sprague-Dawley rats, IL-1beta (500 ng/kg i.v.) rapidly increased oxytocin secretion (3.2-fold), via a central action as the firing rate of oxytocin neurons in the supraoptic nucleus was increased. In contrast, IL-1beta had no significant effect on the electrical or secretory activity of oxytocin neurons in late pregnant rats. In pregnancy activation of a central inhibitory opioid mechanism restrains oxytocin neuron responses to various stimuli. Accordingly, we tested the effects of the opioid antagonist, naloxone, on oxytocin neuron responses to IL-1beta in pregnancy. Naloxone (5 mg/kg i.v.) did not affect the oxytocin secretory response to IL-1beta in virgin rats, whereas in late pregnant rats naloxone revealed a greater oxytocin secretory response to IL-1beta (3.5-fold) than in virgin rats. In virgin rats, naloxone decreased oxytocin neuron firing rate after IL-1beta, however, in pregnant rats naloxone increased the firing rate response to IL-1beta to the level seen in virgin rats. Thus, systemic IL-1beta acts centrally to increase oxytocin secretion. In pregnancy this response is suppressed by endogenous opioids, thus preserving neurohypophysial oxytocin stores for parturition and minimizing the risk of preterm labour. The exaggerated oxytocin secretory response to IL-1beta in pregnancy after naloxone reflects increased oxytocin stores and/or increased efficiency of excitation-secretion coupling at the posterior pituitary.
Brunton
Paula J
PJ
Laboratory of Neuroendocrinology, Centre for Integrative Physiology, College of Medicine and Veterinary Medicine, University of Edinburgh, Hugh Robson Building, George Square, UK.
Sabatier
Nancy
N
Leng
Gareth
G
Russell
John A
JA
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D005260:Female; D007375:Interleukin-1 / Q000276:immunology* / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010121:Oxytocin / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013495:Supraoptic Nucleus / Q000166:cytology
D007375:Interleukin-1; D009292:Narcotic Antagonists; D009294:Narcotics; D009270:Naloxone; D010121:Oxytocin