Central endogenous opioid inhibition of supraoptic oxytocin neurons in pregnant rats.
Naloxone increases oxytocin secretion in pregnant rats, suggesting restraint by endogenous opioids but we have previously reported that oxytocin nerve terminals in the neural lobe become desensitized to opioid actions in late pregnancy. Therefore, we sought evidence for opioid inhibition on oxytocin cell bodies and their inputs at this time. In conscious 21 d pregnant rats naloxone increased the number of neurons expressing Fos (an indicator of neuronal activity) in the supraoptic nucleus (SON) but had no effect on 16 d pregnant or virgin rats. Release of oxytocin within the SON, measured by microdialysis in conscious rats, was also increased by naloxone in late pregnancy but not before. Nor-binaltorphimine, a specific kappa- opioid antagonist, did not increase Fos or affect oxytocin release within the SON in any group. In anesthetized rats the firing rate of SON neurons was recorded and oxytocin neurons identified by an excitatory response to intravenous cholecystokinin. Naloxone potentiated the cholecystokinin-induced firing rate response on day 21 of pregnancy but not in 16 d pregnant or virgin rats. Blood sampling in anesthetized rats showed that naloxone also increased the oxytocin secretory response to cholecystokinin in late pregnant rats. We conclude that in late pregnancy, after day 16, endogenous opioids inhibit oxytocin neurons either directly, on their cell bodies, or presynaptically on inputs. These endogenous opioids do not act through kappa- opioid receptors since nor-binaltorphimine was ineffective, but may act via mu-opioid receptors. Thus, the opioids restrain premature oxytocin secretion until parturition when there is a high demand for it.
Douglas
A J
AJ
Department of Physiology, University Medical School, Edinburgh, United Kingdom.
Neumann
I
I
Meeren
H K
HK
Leng
G
G
Johnstone
L E
LE
Munro
G
G
Russell
J A
JA
D000818:Animals; D001921:Brain / Q000502:physiology*; D002766:Cholecystokinin / Q000494:pharmacology; D004594:Electrophysiology; D004723:Endorphins / Q000502:physiology*; D005260:Female; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009433:Neural Inhibition; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D010121:Oxytocin / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013495:Supraoptic Nucleus / Q000166:cytology / Q000378:metabolism*
D004723:Endorphins; D009292:Narcotic Antagonists; D016760:Proto-Oncogene Proteins c-fos; D009270:Naloxone; D010121:Oxytocin; D002766:Cholecystokinin