Endomorphins and activation of the hypothalamo-pituitary-adrenal axis

Endomorphin (EM)-1 and EM-2 are opioid tetrapeptides recently located in the central nervous system and immune tissues with high selectivity and affinity for the mu-opioid receptor. Intracerebroventricular (i.c.v.) administration of morphine stimulates the hypothalamo-pituitary-adrenal (HPA) axis. The present study investigated the effect of centrally administered EM-1 and EM-2 on HPA axis activation. Rats received a single i.c.v. injection of either EM-1 (0.1, 1.0, 10 microg), EM-2 (10 microg), morphine (10 microg), or vehicle (0.9% saline). Blood samples for plasma corticosterone determinations were taken immediately prior to i.c.v. administration and at various time points up to 4 h post-injection. Trunk blood, brains and pituitaries were collected at 4 h. Intracerebroventricular morphine increased plasma corticosterone levels within 30 min, whereas EM-1 and EM-2 were without effect. In addition, pre-treatment of i.c.v. EM-1 did not block the rise in corticosterone after morphine. Corticotrophin-releasing factor (CRF) mRNA and arginine vasopressin (AVP) mRNA in the paraventricular nucleus (PVN) and POMC mRNA in the anterior pituitary were found to be unaffected by either morphine or endomorphins. Since release of other opioids are elevated in response to acute stress, we exposed rats to a range of stressors to determine whether plasma EM-1 and EM-2 can be stimulated by HPA axis activation. Plasma corticosterone, ACTH and beta-endorphin were elevated following acute restraint stress, but concentrations of plasma EM-1-immunoreactivity (ir) and EM-2-ir did not change significantly. Corticosterone, ACTH and beta-endorphin were further elevated in adjuvant-induced arthritis (AA) rats by a single injection of lipopolysaccharide (LPS), but not by restraint stress. In conclusion, neither EM-1 or EM-2 appear to influence the regulation of the HPA axis. These data suggest that endomorphins may be acting on a different subset of the mu-opioid receptor than morphine. The failure to induce changes in plasma EM-ir in response to the chronic inflammatory stress of AA, the acute immunological stress of LPS, or the psychological stress of restraint, argues against an important role for endomorphins in mediating HPA axis activity.

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Monosodium Glutamate-lnduced Reductions in Hypothalamic Beta-Endorphin Content Result in Mu-Opioid Receptor Upregulation in the Medial Preoptic Area

Neuroendocrinology ◽

10.1159/000126252 ◽

1992 ◽

Vol 56 (3) ◽

pp. 378-384 ◽

Cited By ~ 11

Author(s):

G. Clarissa Desjardins ◽

James R. Brawer ◽

Alain Beaudet

Keyword(s):

Opioid Receptor ◽

Preoptic Area ◽

Monosodium Glutamate ◽

Medial Preoptic Area ◽

Mu Opioid Receptor ◽

Mu Opioid ◽

Beta Endorphin ◽

Receptor Upregulation

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The Influences of Reproductive Status and Acute Stress on the Levels of Phosphorylated Mu Opioid Receptor Immunoreactivity in Rat Hippocampus

Frontiers in Endocrinology ◽

10.3389/fendo.2011.00018 ◽

2011 ◽

Vol 2 ◽

Cited By ~ 10

Author(s):

Keith L. Gonzales ◽

Jeanette D. Chapleau ◽

Joseph P. Pierce ◽

David T. Kelter ◽

Tanya J. Williams ◽

...

Keyword(s):

Opioid Receptor ◽

Acute Stress ◽

Mu Opioid Receptor ◽

Reproductive Status ◽

Rat Hippocampus ◽

Mu Opioid

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Neonatal monosodium glutamate treatment alters both the activity and the sensitivity of the rat hypothalamo-pituitary-adrenocortical axis

Journal of Endocrinology ◽

10.1677/joe.0.1410497 ◽

1994 ◽

Vol 141 (3) ◽

pp. 497-503 ◽

Cited By ~ 23

Author(s):

P J Larsen ◽

J D Mikkelsen ◽

D Jessop ◽

S L Lightman ◽

H S Chowdrey

Keyword(s):

Hpa Axis ◽

Restraint Stress ◽

Acute Stress ◽

Monosodium Glutamate ◽

Plasma Corticosterone ◽

Mrna Levels ◽

Plasma Acth ◽

Corticotrophin Releasing Factor ◽

Acute And Chronic Stress ◽

Corticosterone Response

Abstract We have investigated the effects of monosodium glutamate (MSG) lesioning of the arcuate nucleus on both central and peripheral components of the hypothalamo-pituitary-adrenocortical (HPA) axis under basal conditions and under acute and chronic stress. Plasma ACTH levels were lower in MSG-lesioned rats (27 ± 7 pg/ml) compared with controls (71 ± 18 pg/ml) while corticosterone levels were elevated (523 ± 84 ng/ml compared with 176 ± 34 ng/ml). Quantititative in situ hybridization histochemistry revealed that corticotrophin-releasing factor mRNA levels in the medial parvocellular part of the hypothalamic paraventricular nucleus were significantly lower in MSG-treated rats. MSG lesioning resulted in an enhanced response of corticosterone to restraint stress (1309 ± 92 ng/ml compared with 628 ± 125 ng/ml in sham-lesioned animals), while ACTH responses to restraint stress in MSG-lesioned and sham-MSG groups were not significantly different (160 ± 24 pg/ml and 167 ± 24 pg/ml respectively). These data suggest that MSG-lesioned rats have an increased adrenocortical sensitivity. In rats subjected to the chronic osmotic stimulus of drinking 2% saline for 12 days, plasma ACTH levels were significantly reduced (15 ± 5 pg/ml) and the ACTH and corticosterone responses to restraint stress were eliminated. ACTH levels were also reduced in MSG-treated animals given 2% saline and the ACTH response to acute stress remained absent in these animals. However, a robust corticosterone response to restraint stress was observed in saline-treated MSG-lesioned rats. These data demonstrate that MSG lesioning results in elevated basal and stress-induced plasma corticosterone, and restores the adrenocortical response to stress which is absent in chronically osmotically stimulated rats. The evidence is consistent with the suggestion that MSG lesions a pathway involved in tonic inhibition of the HPA axis. In addition, the adrenocortical sensitivity to ACTH and other secretagogues may be increased in MSG-treated animals. Journal of Endocrinology (1994) 141, 497–503

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Intrahypothalamic Estradiol Modulates Hypothalamus-Pituitary-Adrenal-Axis Activity in Female Rats

Endocrinology ◽

10.1210/en.2011-2176 ◽

2012 ◽

Vol 153 (7) ◽

pp. 3337-3344 ◽

Cited By ~ 27

Author(s):

J. Liu ◽

P. H. Bisschop ◽

L. Eggels ◽

E. Foppen ◽

E. Fliers ◽

...

Keyword(s):

Hpa Axis ◽

Restraint Stress ◽

Acute Stress ◽

Plasma Corticosterone ◽

Female Rats ◽

Ovariectomized Rats ◽

Stress Exposure ◽

Ici 182,780 ◽

Hpa Axis Activity

Estrogen plays an important role in the regulation of the hypothalamus-pituitary-adrenal (HPA)-axis, but the neuroendocrine pathways and the role of estrogen receptor (ER) subtypes involved in specific aspects of this interaction remain unknown. In a first set of experiments, we administered estradiol (E2) intravenously, intracerebroventricularly, and by intrahypothalamic microdialysis to ovariectomized rats to measure plasma corticosterone (CORT) concentrations from carotid artery blood. Systemic infusion of E2 did not increase plasma CORT, but intracerebroventricular E2 induced a 3-fold CORT increase (P = 0.012). Local E2 infusions in the hypothalamic paraventricular nucleus (PVN) significantly increased plasma CORT (P < 0.001). A similar CORT increase was seen after PVN infusion of the ERα agonist propylpyrazoletriol, whereas the ERβ agonist diarylpropiolnitrile had no effect. In a second set of experiments, we investigated whether E2 modulates the HPA-axis response to acute stress by administering E2 agonists or its antagonist ICI 182,780 into the PVN during restraint stress exposure. After 30 min of stress exposure, plasma CORT had increased 5.0-fold (P < 0.001). E2 and propylpyrazoletriol administration in the PVN enhanced the stress-induced plasma CORT increase (8-fold vs. baseline), whereas ICI 182,780 and diarylpropiolnitrile reduced it, as compared with both E2 and vehicle administration in the PVN. In conclusion, central E2 modulates HPA-axis activity both in the basal state and during restraint stress. In the basal condition, the stimulation is mediated by ERα-sensitive neurons, whereas during stress, it is mediated by both ERα and ERβ.

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The Mu-Opioid Receptor Gene Polymorphism (A118G) Alters HPA Axis Activation Induced by Opioid Receptor Blockade

Neuropsychopharmacology ◽

10.1016/s0893-133x(01)00294-9 ◽

2002 ◽

Vol 26 (1) ◽

pp. 106-114 ◽

Cited By ~ 181

Author(s):

G Wand

Keyword(s):

Gene Polymorphism ◽

Opioid Receptor ◽

Hpa Axis ◽

Receptor Gene ◽

Mu Opioid Receptor ◽

Receptor Blockade ◽

Mu Opioid ◽

Receptor Gene Polymorphism

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The vagus nerve is critical for regulation of hypothalamic-pituitary-adrenal axis responses to acute stress

10.1101/2021.06.03.446790 ◽

2021 ◽

Author(s):

Bailey N Keller ◽

Angela E Snyder ◽

Caitlin R Coker ◽

Elizabeth A Aguilar ◽

Mary K O'Brien ◽

...

Keyword(s):

Vagus Nerve ◽

Hpa Axis ◽

Restraint Stress ◽

Acute Stress ◽

Plasma Corticosterone ◽

Action Potential Firing ◽

Acute Restraint Stress ◽

Potential Firing ◽

Crf Neurons ◽

Hpa Function

The hypothalamic pituitary adrenal (HPA) axis is a critical regulator of physiologic and psychological responses to acute and chronic stressors. HPA axis function is control by numerous feedback inhibitory mechanisms, disruptions of which can lead to various psychiatric conditions, such as depression, posttraumatic stress disorder, and schizophrenia. Vagus nerve stimulation has been shown to be efficacious in these various mental health issues potentially via modulation of HPA axis function, but the mechanisms by which the vagus nerve may regulate HPA function has not been fully elucidated. In the present studies, we sought to test the hypothesis that the vagus nerve is a critical regulator of HPA function. Neuroendocrine function and neurocircuit changes in corticotropin releasing factor (CRF) neurons in the paraventricular nucleus of the hypothalamus (PVN) was examined following acute stress after subdiaphragmatic left vagotomy (VX) in adult male Sprague-Dawley rats. We found that VX mimics HPA activation seen in sham surgery animals exposed to acute restraint stress, particularly increased plasma corticosterone levels, elevated PVN CRF mRNA, and increased action potential firing of putative CRF neurons in PVN brain slices. Furthermore, VX animals exposed to acute restraint stress showed increased elevations of plasma corticosterone and PVN CRF mRNA which may be due to lack of compensatory PVN GABAergic signaling in response to acute stress. Both Sham/Stress and VX/no stress conditions increases action potential firing in putative PVN CRF neurons, but this effect was not seen in the VX/stress condition, suggesting that not all forms of stress compensation are lost following VX. Overall, these findings suggest that the vagus nerve may play a critical role in regulating HPA axis function via modulation of local PVN neurocircuit activity.

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