Effect of progesterone on the activation of neurones of the supraoptic nucleus during parturition

Reproduction ◽  
2000 ◽  
pp. 367-376 ◽  
Author(s):  
IA Antonijevic ◽  
JA Russell ◽  
RJ Bicknell ◽  
G Leng ◽  
AJ Douglas
Keyword(s):  
Progesterone Receptor ◽  
Supraoptic Nucleus ◽  
Late Pregnancy ◽  
Endogenous Opioids ◽  
Opioid Antagonist ◽  
Endogenous Opioid ◽  
Fos Expression ◽  
Oxytocin Neurones ◽  
Supraoptic Nuclei

Parturition is driven by a pulsatile pattern of oxytocin secretion, resulting from burst firing activity of supraoptic oxytocin neurones and reflected by induction of Fos expression. Rats were injected with progesterone on day 20 of pregnancy to investigate the role of the decreasing progesterone:ratio oestrogen ratio, which precedes delivery, in the activation of supraoptic neurones. Progesterone delayed the onset of birth by 28 h compared with vehicle (control) and prolonged the duration of delivery, which was overcome by pulsatile injections of oxytocin, indicating that the slow delivery may reflect impaired oxytocin secretion. Parturient rats pretreated with progesterone had fewer Fos immunoreactive nuclei in the supraoptic nucleus than did parturient rats pretreated with vehicle. The number of Fos immunoreactive nuclei was not restored after oxytocin injection, indicating that appropriate activation of oxytocin neurones is impaired by progesterone and also that there is a lack of stimulatory afferent drive. Fos expression increased in the nucleus of the tractus solitarius during parturition in rats pretreated with either vehicle or progesterone, but not in rats that had been pretreated with progesterone and induced with oxytocin, indicating that this input was inhibited. Endogenous opioids inhibit oxytocin neurones in late pregnancy and the opioid antagonist, naloxone, increases Fos expression in supraoptic nuclei by preventing inhibition. However, progesterone attenuated naloxone-induced Fos expression in the supraoptic nucleus in late pregnancy and naloxone administered during parturition did not accelerate the duration of births delayed by progesterone administration, indicating that progesterone does not act by hyperactivation of endogenous opioid tone. RU486, a progesterone receptor antagonist, enhanced supraoptic neurone Fos expression in late pregnancy, indicating progesterone receptor-mediated actions. Thus, progesterone withdrawal is necessary for appropriate activation of supraoptic and tractus solitarius neurones during parturition.

Role of mu 1- and delta-opioid receptors in modulation of fetal EEG and respiratory activity

1993 ◽  
Vol 265 (2) ◽  
pp. R433-R438 ◽  
Author(s):  
P. Y. Cheng ◽  
D. Wu ◽  
Y. Soong ◽  
S. McCabe ◽  
J. A. Decena ◽  
...  
Keyword(s):  
Opioid Receptors ◽  
Respiratory Activity ◽  
Endogenous Opioids ◽  
Opioid Antagonist ◽  
Receptor Subtypes ◽  
Endogenous Opioid ◽  
Eeg Activity ◽  
Delta Opioid Receptors ◽  
Opioid Receptor Subtypes

Recent evidence suggests that administration of low doses of morphine causes respiratory stimulation, along with a more active electroencephalogram (EEG) in the fetal lamb. The present study used selective opioid agonists and antagonists to determine the role mu 1- and delta-opioid receptor subtypes play in the response as well as determine if endogenous opioid peptides exert a tonic influence at the mu 1- and delta-opioid receptors to maintain normal EEG and respiratory activity under control, physiological conditions. Both morphine (2.5 mg/h iv) and [D-Pen2,D-Pen5]enkephalin (DPDPE) (46 nmol/h icv) resulted in a significant activation of fetal EEG, which was blocked by naloxonazine (NALZ, mu 1-opioid antagonist) and naltrindole (NTI, delta-opioid antagonist), respectively. Administration of NALZ alone, but not NTI, resulted in a slowing of the EEG. Morphine and [D-Ala2]deltorphin I (0.36 nmol/h icv) significantly increased breath number and were blocked by NALZ and NTI respectively. Both NALZ and NTI alone resulted in a reduction in breath number. These results suggest that the activation of the delta- or mu 1-opioid receptors will stimulate fetal respiratory and EEG activity. Furthermore, the endogenous opioids play a tonic role at both the delta- and mu 1-opioid receptors in the regulation of respiratory timing and EEG activity.

scholarly journals The importance of oxytocin mechanisms in the control of mouse parturition

Reproduction ◽  
2002 ◽  
pp. 543-552 ◽  
Author(s):  
AJ Douglas ◽  
G Leng ◽  
JA Russell
Keyword(s):  
Red Light ◽  
Endogenous Opioids ◽  
Beta Agonist ◽  
Early Gene ◽  
Opioid Antagonist ◽  
Dependent Manner ◽  
Birth Process ◽  
Opioid Agonist ◽  
Adrenergic Antagonist ◽  
Oxytocin Neurones

The role of oxytocin in parturition in mice was investigated. Pup birth profiles, blood samples and brains were collected from parturient mice observed under red light conditions in a reversed light:dark photoperiod. Peripheral administration of an oxytocin antagonist in a dose-dependent manner delayed the birth of subsequent pups, indicating that oxytocin is required for a normal pup birth profile. Oxytocin neurones were activated during birth as shown by both increased immediate early gene ( Fos) expression in oxytocin neurones in the supraoptic nucleus and increased plasma oxytocin concentrations during birth. In addition, the nucleus of the tractus solitarius and the olfactory bulbs, sites that process inputs to oxytocin neurones, become activated during parturition. Exposure to stress during parturition halted subsequent deliveries; at this stage plasma oxytocin concentrations were not higher than those of virgin mice, and birth was restored by administration of oxytocin. Administration of beta-adrenergic antagonist (propranolol) also restored stress-delayed birth, whereas administration of ritrodrine (beta-agonist) delayed birth in non-stressed mice, indicating that adrenergic mechanisms contribute to stress-delayed births in mice. Administration of morphine (mu-opioid agonist) delayed births transiently, but naloxone (opioid antagonist) did not prevent stress-delayed birth, indicating that endogenous opioids do not appear to contribute to neuroendocrine or uterine mechanisms that promote birth in mice. Therefore, despite evidence in oxytocin knockout mice that oxytocin is not essential for parturition in this species, the results of the present study indicate that oxytocin neurone activity and secretion contribute to the birth process in normal mice.

Regulation of the photoperiod-induced cycle in the peripheral blood concentrations of β-endorphin and prolactin in the ram: role of dopamine and endogenous opioids

1990 ◽  
Vol 127 (3) ◽  
pp. 461-469 ◽  
Author(s):  
E. Ssewannyana ◽  
G. A. Lincoln
Keyword(s):  
Plasma Concentrations ◽  
Prolactin Secretion ◽  
Endogenous Opioids ◽  
Fold Change ◽  
Opioid Antagonist ◽  
Light Cycle ◽  
Blood Concentrations ◽  
The Mean ◽  
Short Days

ABSTRACT In a group of adult Soay rams housed indoors under an artificial light cycle of alternating 16-week periods of long and short days, there was a conspicuous longterm cycle in the peripheral plasma concentrations of β-endorphin and prolactin. The levels of β-endorphin were highest under short days and lowest under long days (15-fold change), and inversely related to the changes in the plasma levels of prolactin (120-fold change). The role of dopamine in the control of β-endorphin and prolactin was investigated in a series of experiments, conducted under both long and short days, in which rams were treated with dopamine receptor agonists (dopamine and bromocriptine) and antagonists (pimozide and sulpiride). Naloxone (opioid antagonist) was also administered to assess the additional involvement of endogenous opioids. Dopamine injected i.v. (6·6 mg/kg every 10 min) did not significantly affect the mean plasma concentrations of β-endorphin and prolactin under either long or short days. Pimozide (0·08 mg/kg i.m. every 2 h) caused a large increase in the mean plasma concentrations of β-endorphin and prolactin under long days but not short days. Naloxone (1·6 mg/kg, i.v.), administered alone or in combination with dopamine or pimozide, had no effect on the mean plasma concentrations of β-endorphin and prolactin, except under short days when, combined with pimozide, it induced an increase in the plasma concentrations of the two polypeptides. Bromocriptine (0·06 mg/kg, s.c.) caused a significant decrease in the plasma concentrations of both β-endorphin and prolactin; this effect was most marked at the times of increased secretion (under short days for β-endorphin and under long days for prolactin). Sulpiride (0·59 mg/kg, s.c.) produced the converse effect and caused an increase in the plasma concentrations of β-endorphin and prolactin with the amplitude and duration of the effect varying with the stage of the photoperiod-induced cycle. From these results in the Soay ram, we conclude that dopamine inhibits β-endorphin and prolactin secretion by way of D2 receptors under both long and short days. Endogenous opioids interact with dopamine, augmenting this inhibition under short days. Differences in the acute responses in the secretion of β-endorphin and prolactin, and the inverse relationship between β-endorphin and prolactin during the cycle, indicate that different regulatory systems involving dopamine influence the two pituitary polypeptides. Journal of Endocrinology (1990) 127, 461–469

Endogenous opioids and ventilatory responses to hypercapnia in normal humans

1985 ◽  
Vol 58 (5) ◽  
pp. 1415-1420 ◽  
Author(s):  
S. E. Weinberger ◽  
R. A. Steinbrook ◽  
D. B. Carr ◽  
E. R. von Gal ◽  
J. E. Fisher ◽  
...  
Keyword(s):  
Opioid Peptides ◽  
Endogenous Opioids ◽  
Opiate Antagonist ◽  
Endogenous Opioid Peptides ◽  
Short Term ◽  
Endogenous Opioid ◽  
Beta Endorphin ◽  
Ventilatory Responses ◽  
Normal Humans

Though administration of opioid peptides depresses ventilation and ventilatory responsiveness, the role of endogenous opioid peptides in modulating ventilatory responsiveness is not clear. We studied the interaction of endogenous opioids and ventilatory responses in 12 adult male volunteers by relating hypercapnic responsiveness to plasma levels of immunoactive beta-endorphin and by administering the opiate antagonist naloxone. Ventilatory responsiveness to hypercapnia was not altered by pretreatment with naloxone, and this by itself suggests that endogenous opioids have no role in modulating this response. However, there was an inverse relationship between basal levels of immunoactive beta-endorphin in plasma and ventilatory responsiveness to CO2. Furthermore, plasma beta-endorphin levels rose after short-term hypercapnia but only when subjects had been pretreated with naloxone. We conclude that measurement of plasma endorphin levels suggests relationships between endogenous opioid peptides and ventilatory responses to CO2 that are not apparent in studies limited to assessing the effect of naloxone.

scholarly journals  The role of beta-endorphin in horses: a review

2011 ◽  
Vol 56 (No. 9) ◽  
pp. 423-429 ◽  
Author(s):  
M. Golynski ◽  
W. Krumrych ◽  
K. Lutnicki
Keyword(s):  
Pain Threshold ◽  
Social Activity ◽  
Prognostic Indicator ◽  
Endogenous Opioids ◽  
Oxygen Species ◽  
Endogenous Opioid System ◽  
Endogenous Opioid ◽  
Beta Endorphin ◽  
Opium Alkaloids

  Opium alkaloids counterparts are secreted by human and animal organisms but the role of endogenous opioid peptides in horses has not yet been fully elucidated. Endogenous opioids are involved in regulating food intake, sexual and social activity, pain relief and pain threshold regulation in horses as well as in regulating the functions of the immune system. The aim of this review is to describe the endogenous opioid system in the horse and its function during stress, illness, reproduction, and its influence on immunity and on the formation of reactive oxygen species (ROS) in horses. What is currently known concerning beta-endorphin suggests that they can be a promising diagnostic or prognostic indicator of many pathologic states in horses.

Opioids in Remote Ischemic Preconditioning-Induced Cardioprotection

2016 ◽  
Vol 22 (2) ◽  
pp. 112-121 ◽  
Author(s):  
Puneet Kaur Randhawa ◽  
Amteshwar Singh Jaggi
Keyword(s):  
Ischemic Preconditioning ◽  
Ischemia Reperfusion ◽  
Artery Bypass ◽  
Bypass Graft ◽  
Endogenous Opioids ◽  
Remote Ischemic Preconditioning ◽  
Endogenous Opioid System ◽  
Endogenous Opioid ◽  
Cardioprotective Effects

Remote ischemic preconditioning (RIPC) is an intriguing process whereby transient regional ischemia and reperfusion episodes to remote tissues including skeletal, renal, mesenteric provide protection to the heart against sustained ischemia–reperfusion-induced injury. Clinically, this technique has been used in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, and heart valve surgery. The endogenous opioid system is extensively expressed in the brain to modulate pain sensation. Besides the role of opioids in relieving pain, numerous researchers have found their critical involvement in evoking cardioprotective effects. Endogenous opioids including endorphins, enkephalins, and dynorphins are released during RIPC and are critically involved in mediating RIPC-induced cardioprotective effects. It has been suggested that during RIPC, the endogenous opioids may be released into the systemic circulation and may travel via bloodstream that act on the myocardial opioid receptors to induce cardioprotection. The present review describes the potential role of opioids in mediating RIPC-induced cardioprotection.

scholarly journals The aetiology of social deficits within mental health disorders: The role of the immune system and endogenous opioids

2019 ◽  
Author(s):  
Sarah Jane Charles ◽  
Miguel Farias ◽  
R. I. M. Dunbar
Keyword(s):  
Mental Health ◽  
Immune System ◽  
Mental Health Disorders ◽  
Social Bonding ◽  
Endogenous Opioids ◽  
Future Research ◽  
Endogenous Opioid System ◽  
Endogenous Opioid ◽  
Health Disorders

The American National Institute for Mental Health (NIMH) has put out a set of research goals that include a long-term plan to identify more reliable endogenous explanations for a wide variety of mental health disorders (Insel, 2013). In response to this, we have identified a major symptom that underlies multiple mental health disorders – social bonding dysfunction. We suggest that endogenous opioid abnormalities can lead to altered social bonding, which is a symptom of various mental health disorders, including depression, schizophrenia and ASD. This article first outlines how endogenous opioids play a role in social bonding. Then we show their association with the body’s inflammation immune function, and review recent literature linking inflammation to mental health ‘immunophenotypes’. We finish by explaining how these immunophenotypes may be caused by alterations in the endogenous opioid system. This is the first overview of the role of inflammation across multiple disorders where we provide a biochemical explanation for why immunophenotypes might exist across diagnoses. We propose a novel mechanism of how the immune system may be causing ‘sickness-type’ behaviours (fatigue, appetite change, social withdrawal and inhibited motivation) in those who have these immunophenotypes. We hope that this novel aetiology can be used as a basis for future research in mental health.

Mediation of stress-induced inhibition of oxytocin in farrowing sows by endogenous opioids

1992 ◽  
Vol 1992 ◽  
pp. 56-56 ◽  
Author(s):  
A. B. Lawrence ◽  
J. C. Petherick ◽  
K. Mclean ◽  
C. Gilbert
Keyword(s):  
Acute Stress ◽  
Endogenous Opioids ◽  
Opioid Antagonist ◽  
Large Animal Model ◽  
Large Animal ◽  
Environmental Disturbance ◽  
Endocrine Control ◽  
Birth Intervals ◽  
Commercial Farming

A considerable amount is now known about the endocrine and neuro-endocrine control of parturition. Far less is understood however about the effect of events which may be considered stressful on the parturition process, despite its broad relevance to animal welfare and farm animal production. There is evidence that stress can have highly disruptive effects during parturition. For example, it has been suggested, that in pigs the behaviourally restricting farrowing crates used in commercial farming practice give rise to increased inter-piglet birth intervals and piglet mortality (Vestergaard and Hansen, 1984). Recent work on rodents has suggested that inhibtion of oxytocin secretion mediated by endogenous opioids, might be responsible for prolonged parturition following an acute stress such as a mid-partum change of environment. The aim of the present work was to extend the study of the effects of stress at parturition to a large animal model. We report two studies on the effects on parturition and oxytocin secretion of movement in mid-parturition to a novel environment (environmental disturbance). In Experiment 1 the effect of this disturbance on inter-piglet interval was investigated. In Experiment 2 a fuller investigation was made of the effects of environmental disturbance on a range of measures including inter-birth interval, behaviour of the sow and plasma oxytocin and Cortisol levels. The role of opioids was investigated in both experiments by administration of the opioid antagonist naloxone.

Opioids and breathing

1985 ◽  
Vol 59 (6) ◽  
pp. 1675-1685 ◽  
Author(s):  
T. V. Santiago ◽  
N. H. Edelman
Keyword(s):  
Pain Modulation ◽  
Endogenous Opioids ◽  
Opiate Antagonist ◽  
Endogenous Opioid ◽  
Disease States ◽  
Specific Effects ◽  
Neonatal Life ◽  
Opiate Drugs ◽  
Recent Developments

This review summarizes recent developments on the effects of opiate drugs and the various endogenous opioid peptides on breathing. These developments include demonstration of receptors and site-specific effects of application of opioids in the pons and medulla, demonstration of variable tolerance of respiratory responses in addicted individuals as well as their offspring, and demonstration of an endogenous opioid influence on breathing in early neonatal life and in certain physiological settings and disease states. The validity and limitations of using naloxone as a tool to uncover postulated endogenous opioid influences are also discussed as well as the potential problems imposed by the various settings in which this opiate antagonist drug is used. It is concluded that some parallelism exists between the role of endogenous opioids in pain modulation and their role in respiration especially in adults. Although more studies are needed especially with regard to defining specific effects of the various opioid receptors and ligands, it is felt that the effects of endogenous opioids on the control of breathing will probably be one of modulating the responses to drugs or nociceptive respiratory stimuli through inhibitory pathways.

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