scholarly journals Regulation by endogenous opioids of suckling-induced prolactin secretion in pregnant and lactating rats: role of ovarian steroids

2002 ◽  
Vol 172 (2) ◽  
pp. 255-261 ◽  
Author(s):  
M Soaje ◽  
EG de Di Nasso ◽  
RP Deis
Keyword(s):  
Inhibitory Effect ◽  
Prolactin Secretion ◽  
Endogenous Opioids ◽  
Opioid System ◽  
Serum Prolactin ◽  
Endogenous Opioid Peptides ◽  
Endogenous Opioid ◽  
Subsequent Increase ◽  
Stimulatory Action

Evidence suggests that endogenous opioid peptides are implicated in the suckling-induced prolactin rise. We explored the role of the opioid system and the participation of ovarian hormones in the regulation of prolactin induced by the suckling stimulus at the end of pregnancy in rats with developed maternal behavior, and during lactation. Suckling for 24 h induced a significant increase in serum prolactin on day 19 of pregnancy, which was increased more than three times when naloxone (2 mg/kg s.c.) or mifepristone (2 mg/kg) was administered. The combination of naloxone and mifepristone did not increase serum prolactin more than either compound alone. Administration of tamoxifen (500 microg/kg orally) on days 14 and 15 of pregnancy completely abolished the effect of naloxone, indicating a role for estrogens in establishing this inhibitory role of opioids. To examine the participation of the opioid system during lactation, we used groups of rats on days 1, 3, 5, 12 and 19 postpartum either (i) isolated from the pups for 4 h, or (ii) isolated from the pups for 3.5 h and reunited with them and suckled for 30 min. Naloxone, given just before replacing the pups, prevented the increase in serum prolactin levels observed in the suckled group of rats but had no effect on the basal levels of the isolated rats. To examine whether the participation of the opioid system in the release of prolactin is dependent on the variation of progesterone levels, rats on day 20 of pregnancy were implanted with two cannulae containing progesterone (that blocked postpartum ovulation) or cholesterol, and cesarean surgery was performed on day 21. To maintain lactation, pups (1-3 days old) were replaced every 24 h, and 4 days after the cesarean eight pups were placed in the cage at 1800 h to maintain a strong suckling stimulus during the following 24 h. Naloxone administration significantly reduced serum prolactin levels in control (cholesterol) rats but progesterone implants prevented the inhibitory effect of naloxone and this effect was not modified by treatment with estrogen. These results indicate that the opioid system modulates suckling-induced prolactin secretion, passing from an inhibitory action before delivery to a stimulatory action during lactation. This regulatory shift seems to be dependent on the fall in progesterone concentration at the end of pregnancy and the subsequent increase after the postpartum ovulation and luteal phase.

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.

Opioidergic regulation of prolactin secretion during pregnancy: role of ovarian hormones

1997 ◽  
Vol 155 (1) ◽  
pp. 99-106 ◽  
Author(s):  
M Soaje ◽  
RP Deis
Keyword(s):  
Ovarian Hormones ◽  
Prolactin Secretion ◽  
High Serum ◽  
Opioid System ◽  
Serum Prolactin ◽  
Stimulatory Action ◽  
Serum Progesterone ◽  
Naloxone Administration ◽  
Ru 486 ◽  
Naloxone Treatment

We have recently demonstrated the existence of a neuromodulatory regulation of prolactin secretion by the opioid system showing a paradoxical opioid-induced prolactin suppression at the end of pregnancy. The aim of this study was to determine a possible interaction between the opioid system and ovarian hormones on the release of prolactin during pregnancy. Serum prolactin levels measured at 1800 h were significantly higher on days 3 and 6 of pregnancy when compared with the other days of gestation. These increases in serum prolactin were reduced significantly by naloxone (2 mg/kg) administered at 1730 h and by RU-486 (10 mg/kg) administered at 0800 h. The response induced by RU-486 was potentiated by naloxone only on day 3. On days 7, 13 and 16, prolactin secretion was not modified by RU-486 and/or naloxone treatment. In RU-486 pretreated rats, naloxone administration increased serum prolactin levels only on day 16 of pregnancy. Interestingly, progesterone treatment (0.5 mg/rat) on days 13, 14 and 15 of pregnancy prevented the high increase in serum prolactin induced by RU-486 and naloxone on day 16 of pregnancy. The progressive increase and decrease of serum progesterone concentration during pregnancy was not modified by naloxone treatment. The participation of oestrogen in the regulation of prolactin secretion by the opioid system on days 3, 16 and 19 was examined by treating these groups of rats with oestradiol benzoate or tamoxifen citrate. Oestradiol (2 micrograms/rat) significantly increased serum prolactin levels on day 3 and naloxone administration did not modify this increase. No effect was observed after oestradiol (5 micrograms/rat) and naloxone treatment on days 16 and 19 of pregnancy. Oral administration of tamoxifen (500 micrograms/kg) the previous day did not modify the serum prolactin concentration measured at 1800 h in oil-treated rats on days 3, 16 and 19 of pregnancy. The antioestrogen completely abolished the naloxone-induced prolactin secretion on day 16 in rats pretreated with RU-486 but no effect was observed on day 19. When tamoxifen was administered on days 14 and 15 of pregnancy, the high serum prolactin levels on day 19 induced by treatment with RU-486 and naloxone were significantly reduced. In conclusion, these results provide an important new insight into the existence of a dual neuromodulatory regulation of prolactin secretion by the opioid system during pregnancy. After a stimulatory action during the first days, there is a change to an inhibitory control at the end of pregnancy, starting around day 16. Moreover, the activation of the inhibitory modulation of the opioid system on prolactin secretion on days 16 and 19 of pregnancy seems to be mediated by changes in the oestrogen and progesterone action.

scholarly journals The role of mu-opioids for reward and threat processing in humans: Bridging the gap from preclinical to clinical opioid drug studies

2021 ◽  
Author(s):  
Isabell M. Meier ◽  
Marie Eikemo ◽  
Siri Leknes
Keyword(s):  
Human Brain ◽  
Emotional Learning ◽  
Endogenous Opioids ◽  
Opioid System ◽  
Opioid Misuse ◽  
Opioid Use ◽  
Endogenous Opioid ◽  
Mu Opioid ◽  
Threat Processing

Purpose of review. Opioid receptors are widely expressed in the human brain. A number of features commonly associated with drug use disorder, such as difficulties in emotional learning, emotion regulation & anhedonia, have been linked to endogenous opioid signaling. Whereas chronic substance use and misuse are thought to alter the function of the mu-opioid system, the specific mechanisms are not well understood. We argue that understanding exogenous and endogenous opioid effects in the healthy human brain is an essential foundation for bridging preclinical and clinical findings related to opioid misuse. Here, we will examine psychopharmacological evidence to outline the role of the mu-opioid receptor (MOR) system in the processing of threat and reward, and discuss how disruption of these processes by chronic opioid use might alter emotional learning and reward responsiveness.Recent findings. In healthy people, studies using opioid antagonist drugs indicate that the brain’s endogenous opioids downregulate fear reactivity and upregulate learning from safety. At the same time, endogenous opioids increase the liking of and motivation to engage with high reward value cues. Studies of acute opioid agonist effects indicate that with non-sedative doses, drugs such as morphine and buprenorphine can mimic endogenous opioid effects on liking and wanting. Disruption of endogenous opioid signalling due to prolonged opioid exposure is associated with some degree of anhedonia to non-drug rewards; however new results leave open the possibility that this is not directly opioid-mediated.Summary. The available human psychopharmacological evidence indicates that the healthy mu-opioid system contributes to the regulation of reward and threat processing. Overall, endogenous opioids can subtly increase liking and wanting responses to a wide variety of re-wards, from sweet tastes to feelings of being connected to close others. For threat related processing, human evidence suggests that endogenous opioids inhibit fear conditioning and reduce the sensitivity to aversive stimuli, although inconsistencies remain. The size of effects reported in healthy humans are however modest, clearly indicating that MORs play out their role in close concert with other neurotransmitter systems. Relevant candidate systems for future re-search include dopamine, serotonin and endocannabinoid signalling. Nevertheless, it is possible that endogenous opioid fine-tuning of reward and threat processing, when unbalanced by e.g. opioid misuse, could over time develop into symptoms associated with opioid use disorder, such as anhedonia and depression/anxiety.

Modulation of luteinizing hormone receptors: effect of an inhibitor of prolactin secretion, p-coumaric acid

1983 ◽  
Vol 98 (3) ◽  
pp. 307-311 ◽  
Author(s):  
Mridula Chowdhury ◽  
S. N. Kabir ◽  
A. K. Pal ◽  
Anita Pakrashi
Keyword(s):  
Hormone Receptors ◽  
Complete Recovery ◽  
Inhibitory Effect ◽  
Prolactin Secretion ◽  
Serum Prolactin ◽  
Affinity Constant ◽  
Scatchard Analysis ◽  
Coumaric Acid ◽  
Binding Data

Daily oral administration of p-coumaric acid (PCA) at a dose of 50 mg/kg body wt for 21 days to adult male mice caused a dramatic reduction in serum prolactin concentrations. A significant fall in testicular LH binding was also observed after PCA treatment. Complete recovery of testicular LH binding was obtained by daily administration of prolactin (500 μg/mouse) when given simultaneously from day 9 of PCA treatment. A lower daily dose of prolactin (250 μg) was found to be ineffective. Scatchard analysis of binding data suggested a decrease in the number of testicular LH binding sites after PCA treatment whereas the affinity constant was unchanged. These results provide direct evidence for an inhibitory effect of PCA on prolactin secretion and also provide additional evidence in favour of a role of prolactin in the modulation of LH receptors.

Opioid modulation of FSH, growth hormone and prolactin secretion in the prepuberal gilt

1992 ◽  
Vol 133 (1) ◽  
pp. 13-19 ◽  
Author(s):  
C. R. Barb ◽  
R. R. Kraeling ◽  
G. B. Rampacek
Keyword(s):  
Body Weight ◽  
Prolactin Secretion ◽  
Morphine Treatment ◽  
Endogenous Opioid Peptides ◽  
Endogenous Opioid ◽  
Gh Secretion ◽  
Age Related ◽  
Artificial Cerebrospinal Fluid ◽  
Serum Gh

ABSTRACT The role of endogenous opioid peptides (EOP) in modulating GH, prolactin (PRL) and FSH secretion was evaluated in prepuberal (P) gilts. In experiment I, P gilts received 1 (n = 2), 3 (n = 3) or 6 (n = 3) mg naloxone (NAL)/kg body weight i.v. Blood was collected every 15 min for 2 h prior to and 2 h after NAL and an additional 1 h after 100 μg gonadotrophinreleasing hormone (GnRH) i.v. In experiment II, P and mature (M) gilts were ovariectomized. Three weeks after ovariectomy, P and M gilts were injected twice a day for 10 days with either 0·85 mg progesterone (P4)/kg body weight or oil vehicle (V), resulting in the following groups: PP4 (n=11), PV (n = 10), MP4 (n=11) and MV (n=10). All gilts received 1 mg NAL/kg body weight on the last day of treatment. Blood samples were collected every 15 min for 4 h before and 2 h after NAL and an additional 1 h after 100μg GnRH i.v. In experiment III, six P and five M gilts were ovariectomized and surgically implanted with intracerebroventricular (i.c.v.) cannulae. Blood was collected every 15 min for 3 h before and 3 h after i.c.v. injection of 500 μg morphine in artificial cerebrospinal fluid (CSF) or 250 μl CSF. In experiment I, all doses of NAL failed to alter PRL secretion, while NAL increased (P<0·05) GH secretion in three out of eight gilts. However, NAL suppressed (P <0·05) FSH concentrations. In experiment II, NAL treatment increased (P<0·01) serum PRL concentrations and suppressed (P <0·05) FSH secretion in MP4 gilts. Serum PRL and FSH concentrations were unaltered by NAL in PV, PP4 and MV gilts. In experiment III, mean serum GH, PRL and FSH concentrations were unaffected by CSF injections. Morphine treatment evoked a rapid increase in serum GH and PRL concentrations in both P and M gilts. In contrast, morphine failed to influence FSH secretion in P gilts but did suppress FSH concentrations in M gilts. These data suggest that EOP receptors are functionally coupled to the GH and PRL secretory systems. There is an age-related change in EOP modulation of PRL secretion, while EOP modulation of FSH secretion is an age- and ovarian-dependent process. Journal of Endocrinology (1992) 133, 13–19

The neuroendocrine paraventricular hypothalamus: receptors, signal transduction, mRNA and neurosecretion

1988 ◽  
Vol 139 (1) ◽  
pp. 31-49
Author(s):  
S. L. Lightman
Keyword(s):  
Nervous System ◽  
Median Eminence ◽  
Opioid Peptides ◽  
Hormone Secretion ◽  
Endogenous Opioids ◽  
Pituitary Hormone ◽  
Endogenous Opioid Peptides ◽  
Endogenous Opioid ◽  
Corticotrophin Releasing Factor

The hypothalamus is one of the most studied areas of the central nervous system. Many of its functions are understood and there is an extensive literature on its role in the control of pituitary hormone secretion, autonomic nervous system activity, regulation of salt, water and food ingestion, body temperature regulation and aspects of behaviour. Although the role of the hypothalamus in the control of pituitary secretion was postulated in the early 1900s, the chemical nature of these control mechanisms has only been documented in the last few years. The opioid peptides represent one particular family of chemical compounds which have been shown to have many effects on pituitary hormone secretion. Exogenous opioids inhibit the neurosecretion of both vasopressin and oxytocin from the posterior pituitary neurosecretory terminals of hypothalamic cell bodies. Opioids also have major actions on the secretory activity of the anterior pituitary which has no innervation from the hypothalamus, but which is regulated by blood-borne factors in the hypophyseal portal circulation which runs from the median eminence of the hypothalamus. It was therefore of considerable interest when it was discovered that endogenous opioid peptides could be detected both in the neurohypophyseal system and in cells which project into the median eminence. The simple presence of a peptide in a neurone does not necessarily imply a function. If, however, we can demonstrate that regulation of the synthesis of the peptide occurs in a manner which corresponds with the expected role of the agent, this provides powerful data in support of a genuine physiological function. The elucidation of the genomic structure of the precursors for the three endogenous opioid peptides has provided us with the ability to measure mRNA for these peptides in defined areas of the brain and to assess their response to appropriate stimuli. Not only does mRNA for the endogenous opioid dynorphin coexist in the same cells as vasopressin but we have now been able to demonstrate that stimuli to vasopressin secretion also result in a markedly increased accumulation of dynorphin mRNA. Similarly, previous studies have shown that opioid peptides derived from another precursor--pro-enkephalin A--coexist with corticotrophin releasing factor in a different group of hypothalamic cells. We have now been able to demonstrate that stresses which result in an accumulation of corticotrophin releasing factor mRNA also result in increased pro-enkephalin mRNA in the same area. This considerably strengthens the hypothesis that endogenous opioids do play a significant role in the control of hypophyseal secretion.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals The Role of Mu-Opioids for Reward and Threat Processing in Humans: Bridging the Gap from Preclinical to Clinical Opioid Drug Studies

2021 ◽  
Author(s):  
Isabell M. Meier ◽  
Marie Eikemo ◽  
Siri Leknes
Keyword(s):  
Human Brain ◽  
Emotional Learning ◽  
Endogenous Opioids ◽  
Opioid System ◽  
Opioid Misuse ◽  
Opioid Use ◽  
Endogenous Opioid ◽  
Mu Opioid ◽  
Threat Processing

Abstract Purpose of Review Opioid receptors are widely expressed in the human brain. A number of features commonly associated with drug use disorder, such as difficulties in emotional learning, emotion regulation and anhedonia, have been linked to endogenous opioid signalling. Whereas chronic substance use and misuse are thought to alter the function of the mu-opioid system, the specific mechanisms are not well understood. We argue that understanding exogenous and endogenous opioid effects in the healthy human brain is an essential foundation for bridging preclinical and clinical findings related to opioid misuse. Here, we will examine psychopharmacological evidence to outline the role of the mu-opioid receptor (MOR) system in the processing of threat and reward, and discuss how disruption of these processes by chronic opioid use might alter emotional learning and reward responsiveness. Recent Findings In healthy people, studies using opioid antagonist drugs indicate that the brain’s endogenous opioids downregulate fear reactivity and upregulate learning from safety. At the same time, endogenous opioids increase the liking of and motivation to engage with high reward value cues. Studies of acute opioid agonist effects indicate that with non-sedative doses, drugs such as morphine and buprenorphine can mimic endogenous opioid effects on liking and wanting. Disruption of endogenous opioid signalling due to prolonged opioid exposure is associated with some degree of anhedonia to non-drug rewards; however, new results leave open the possibility that this is not directly opioid-mediated. Summary The available human psychopharmacological evidence indicates that the healthy mu-opioid system contributes to the regulation of reward and threat processing. Overall, endogenous opioids can subtly increase liking and wanting responses to a wide variety of rewards, from sweet tastes to feelings of being connected to close others. For threat-related processing, human evidence suggests that endogenous opioids inhibit fear conditioning and reduce the sensitivity to aversive stimuli, although inconsistencies remain. The size of effects reported in healthy humans are however modest, clearly indicating that MORs play out their role in close concert with other neurotransmitter systems. Relevant candidate systems for future research include dopamine, serotonin and endocannabinoid signalling. Nevertheless, it is possible that endogenous opioid fine-tuning of reward and threat processing, when unbalanced by e.g. opioid misuse, could over time develop into symptoms associated with opioid use disorder, such as anhedonia and depression/anxiety.

Role of the endogenous opioid system in the analgesic effect of ?-tocopherol in dysmenorrhea

1988 ◽  
Vol 105 (2) ◽  
pp. 162-164 ◽  
Author(s):  
G. N. Kryzhanovskii ◽  
L. P. Bakuleva ◽  
N. L. Luzina ◽  
V. A. Vinogradov ◽  
K. N. Yarygin ◽  
...  
Keyword(s):  
Analgesic Effect ◽  
Opioid System ◽  
Endogenous Opioid System ◽  
Endogenous Opioid

Genetics of alcoholism: Role of the endogenous opioid system

1994 ◽  
Vol 9 (2) ◽  
pp. 105-131 ◽  
Author(s):  
Christina Gianoulakis ◽  
Jean-Pascal de Waele
Keyword(s):  
Opioid System ◽  
Endogenous Opioid System ◽  
Endogenous Opioid
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