Effects of alprazolam on cholecystokinin-tetrapeptide (CCK-4) induced panic and hypothalamic-pituitary-adrenal (HPA) axis activity

2004 ◽  
Vol 36 (05) ◽  
Author(s):  
D Eser ◽  
P Zwanzger ◽  
S Aicher ◽  
C Schüle ◽  
TC Baghai ◽  
...  
2013 ◽  
Vol 219 (1) ◽  
pp. 21-27 ◽  
Author(s):  
Nathalie Marissal-Arvy ◽  
Rachel Hamiani ◽  
Emmanuel Richard ◽  
Marie-Pierre Moisan ◽  
Véronique Pallet

The aim of this study was to explore the involvement of retinoids in the hypoactivity and hyporeactivity to stress of the hypothalamic–pituitary–adrenal (HPA) axis in LOU/C rats. We measured the effects of vitamin A deficiency administered or not with retinoic acid (RA) on plasma corticosterone in standard conditions and in response to restraint stress and on hypothalamic and hippocampal expression of corticosteroid receptors, corticotropin-releasing hormone and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in LOU/C rats. Interestingly, under control conditions, we measured a higher plasma concentration of retinol in LOU/C than in Wistar rats, which could contribute to the lower basal activity of the HPA axis in LOU/C rats. Vitamin A deficiency induced an increased HPA axis activity in LOU/C rats, normalized by RA administration. Compared with LOU/C control rats, vitamin A-deficient rats showed a delayed and heightened corticosterone response to restraint stress. The expression of corticosteroid receptors was strongly decreased by vitamin A deficiency in the hippocampus, which could contribute to a less efficient feedback by corticosterone on HPA axis tone. The expression of 11β-HSD1 was increased by vitamin A deficiency in the hypothalamus (+62.5%) as in the hippocampus (+104.7%), which could lead to a higher production of corticosterone locally and contribute to alteration of the hippocampus. RA supplementation treatment restored corticosterone concentrations and 11β-HSD1 expression to control levels. The high vitamin A status of LOU/C rats could contribute to their low HPA axis activity/reactivity and to a protective effect against 11β-HSD1-mediated deleterious action on cognitive performances during ageing.


2013 ◽  
Vol 304 (10) ◽  
pp. E1105-E1117 ◽  
Author(s):  
Manuel Gil-Lozano ◽  
Marina Romaní-Pérez ◽  
Verónica Outeiriño-Iglesias ◽  
Eva Vigo ◽  
Patricia L. Brubaker ◽  
...  

Exendin-4 (Ex-4) is a natural agonist of the glucagon-like peptide-1 (GLP-1) receptor, currently being used as a treatment for type 2 diabetes mellitus due to its insulinotropic properties. Previous studies have revealed that acute administration of both GLP-1 and, in particular, Ex-4 potently stimulates hypothalamic-pituitary-adrenal (HPA) axis activity. In this work, the effects of prolonged Ex-4 exposure on HPA function were explored. To this end, Sprague-Dawley rats were subjected to a daily regimen of two Ex-4 injections (5 μg/kg sc) for a minimum of 7 days. We found that subchronic Ex-4 administration produced a number of effects that resemble chronic stress situations, including hyperactivation of the HPA axis during the trough hours, disruption of glucocorticoid circadian secretion, hypertrophy of the adrenal gland, decreased adrenal gland sensitivity, impaired pituitary-adrenal stress responses, and reductions in both food intake and body weight. In addition, a threefold increase in diuresis was observed followed by a 1.5-fold increase in water intake; these latter effects were abolished by adrenalectomy. Together, these findings indicate that Ex-4 induces a profound dysregulation of HPA axis activity that may also affect renal function.


Author(s):  
Greti Aguilera

AbstractThe major endocrine response to stress occurs via activation of the hypothalamic-pituitary-adrenal (HPA) axis, leading ultimately to increases in circulating glucocorticoids, which are essential for the metabolic adaptation to stress. The major players in the HPA axis are the hypothalamic neuropeptide, corticotropin releasing hormone (CRH), the pituitary hormone adrenocorticotropic hormone, and the negative feedback effects of adrenal glucocorticoids. In addition, a number of other neuropeptides, including vasopressin (VP), angiotensin II, oxytocin, pituitary adenylate cyclase activating peptide, orexin and cholecystokinin, and nesfatin can affect HPA axis activity by influencing the expression and secretion of CRH, and also by modulating pituitary corticotroph function or adrenal steroidogenesis. Of these peptides, VP co-secreted with CRH from axonal terminals in the external zone of the median eminence plays a prominent role by potentiating the stimulatory effect of CRH and by increasing the number of pituitary corticotrophs during chronic challenge. Although the precise role and significance of many of these neuropeptides in regulating HPA axis activity requires further investigation, it is likely that they are part of a multifactorial system mediating the fine tuning of HPA axis activity during adaptation to a variety of physiological and stressful conditions.


2005 ◽  
Vol 152 (2) ◽  
pp. 249-253 ◽  
Author(s):  
Rebecca M Reynolds ◽  
Brian R Walker ◽  
Holly E Syddall ◽  
Ruth Andrew ◽  
Peter J Wood ◽  
...  

Objective: Increased hypothalamic–pituitary–adrenal (HPA) axis activity in men of low birthweight may be an important link between early life and the adult metabolic syndrome. In animal models females are more sensitive than males to HPA axis programming, but whether gender influences susceptibility in humans is unknown. Design: Birth cohort study. Methods: We studied 106 women aged 67–78 years, from Hertfordshire, UK, in whom birthweight was recorded. Negative feedback sensitivity was assessed by an overnight low-dose (0.25 mg) dexa-methasone suppression test, and adrenal sensitivity by a low-dose (1 μg) ACTH1 – 24 stimulation test. Cortisol and its metabolites were analysed in a 24 h urine collection. Data were compared with previously published identical measurements in 205 men aged 66–77 years from the same cohort. Results: In women, plasma cortisol levels after dexamethasone were lower (P < 0.0001) and peak cortisol following ACTH1 – 24 were higher (P < 0.0001) than in men, suggesting a more responsive HPA axis. As in men, women with lower birthweight had enhanced plasma cortisol responses to ACTH1 – 24 (P = 0.05 for trend) but no difference in plasma cortisol after dexamethasone or in urinary cortisol metabolite excretion. The strength of the association in women was not different from that in men; a 1 lb decrease in birthweight was associated with an incremental rise in cortisol of 12.6 nmol/l (95% confidence interval (CI) 1.4, 23.8) in men, P = 0.03, and 14.8 nmol/l (95% CI −0.4, 29.9) in women, P = 0.05 (P = 0.82 for birthweight × gender interaction). In a combined analysis of men and women adjusted for gender (n = 302), a 1 lb decrease in birthweight was associated with a 13.4 nmol/l (95% CI 4.5, 22.4) greater incremental rise in plasma cortisol, P = 0.003. Conclusions: Associations between lower birthweight and increased HPA axis activity are similar in men and women, supporting the hypothesis that HPA axis activation is an important mechanism underlying programming of adult disease.


2017 ◽  
Vol 43 (4) ◽  
pp. 353-365 ◽  
Author(s):  
Maria A Gartstein ◽  
Erich Seamon ◽  
Stephanie F Thompson ◽  
Liliana J Lengua

Abstract Objective Identification of early risk factors related to obesity is critical to preventative public health efforts. In this study, we investigated links between the Hypothalamic–Pituitary–Adrenal (HPA)-axis activity (diurnal cortisol pattern), geospatially operationalized exposure to neighborhood crime, and body mass index (BMI) for a sample of 5-year-old children. Greater community crime exposure and lower HPA-axis activity were hypothesized to contribute to higher BMI, with child HPA-axis moderating the association between crime exposure and BMI. Method Families residing within the boundaries of the City of Seattle (N = 114) provided information concerning demographic/psychosocial risk factors, used to calculate a Cumulative Risk Index, indicating the number of contextual adversities present. Child BMI and diurnal cortisol pattern (derived from assays of saliva samples) were examined, along with neighborhood crime indices computed with publically available information, based on participants’ locations. Results Hierarchical multiple regression analyses, adjusted for covariates (cumulative risk, age, and sex), indicated that crime proximity made a unique contribution to child BMI, in the direction signaling an increase in the risk for obesity. Consistent with our hypothesis, a significant interaction was observed, indicative of moderation by diurnal cortisol pattern. Follow-up simple slope analyses demonstrated that crime exposure was significantly related to higher BMI for children with low-flat (blunted) diurnal cortisol patterns, where community crime and BMI were not significantly associated at higher levels of cortisol. Conclusion Community crime exposure contributes to higher BMI as early as the preschool period, and blunted diurnal cortisol patterns may place children experiencing neighborhood adversity at greater risk for obesity.


2006 ◽  
Vol 290 (5) ◽  
pp. R1366-R1373 ◽  
Author(s):  
Jennifer A. Shoener ◽  
Romana Baig ◽  
Kathleen C. Page

Glucocorticoids are essential for normal hypothalamic-pituitary-adrenal (HPA) axis activity; however, recent studies warn that exposure to excess endogenous or synthetic glucocorticoid during a specific period of prenatal development adversely affects HPA axis stability. We administered dexamethasone (DEX) to pregnant rats during the last week of gestation and investigated subsequent HPA axis regulation in adult male offspring in unrestrained and restraint-stressed conditions. With the use of real-time PCR and RIA, we examined the expression of regulatory genes in the hippocampus, hypothalamus, and pituitary, including corticotropin-releasing hormone (CRH), arginine vasopressin (AVP), glucocorticoid receptors (GR), mineralcorticoid receptors (MR), and 11-β-hydroxysteroid dehydrogenase-1 (11β-HSD-1), as well as the main HPA axis hormones, adrenal corticotropic hormone (ACTH) and corticosterone (CORT). Our results demonstrate that the DEX-exposed group exhibited an overall change in the pattern of gene expression and hormone levels in the unrestrained animals. These changes included an upregulation of CRH in the hypothalamus, a downregulation of MR with a concomitant upregulation of 11β-HSD-1 in the hippocampus, and an increase in circulating levels of both ACTH and CORT relative to unrestrained control animals. Interestingly, both DEX-exposed and control rats exhibited an increase in pituitary GR mRNA levels following a 1-h recovery from restraint stress; however, the increased expression in DEX-exposed rats was significantly less and was associated with a slower return to baseline CORT compared with controls. In addition, circulating levels of ACTH and CORT as well as hypothalamic CRH and hippocampal 11β-HSD-1 expression levels were significantly higher in the DEX-exposed group compared with controls following restraint stress. Taken together, these data demonstrate that late-gestation DEX exposure in rats is associated with persistent changes in both the modulation of HPA axis activity and the HPA axis-mediated response to stress.


1994 ◽  
Vol 24 (1) ◽  
pp. 167-177 ◽  
Author(s):  
M. Maes ◽  
H. Y. Meltzer ◽  
W. Stevens ◽  
P. Cosyns ◽  
P. Blockx

SynopsisMajor depression is reportedly characterized by increased activity of the hypothalamic–pituitary–adrenal (HPA) axis and by in vivo immune activation. The present study was carried out in order to investigate the relationships between HPA-axis activity and in vivo immune function in depression. Towards this end the following parameters were measured: 24 h urinary cortisol (UC) excretion; basal and post-dexamethasone (DST) plasma cortisol, β-endorphin/β-lipotropin (βEND/βLPH) and dexamethasone concentrations; and leucocyte subsets (i.e. lymphocytes, neutrophils, monocytes, CD4+, CD4+CD45RA+, CD4+CD45RO+, CD8+, CD8+CD57+, CD8+CD57−, HLA-DR+, CD25+ T cells, HLA-DR+, CD19+, CD20+, and CD21+ B cells) both pre-and post-DST. Dexamethasone administration (1 mg orally) induced leucocytosis, lymphocytopaenia, monocytopaenia and neutrophilia. HPA-axis non-suppressors exhibited a relative resistance to the enhancing (e.g. neutrophils) or depressant (e.g. lymphocytes, CD4+ T cells) effects of dexamethasone. There were significant correlations between UC excretion and the number of percentage of lymphocytes, monocytes, CD4+CD45RA+ and CD8+CD57− T cells (negatively) and neutrophils (positively). It is concluded that multiple and complex intertwined relationships between HPA-axis hyperactivity and systemic immune stimulation participate in the pathophysiology or pathogenesis of major depression.


1999 ◽  
pp. 130-136 ◽  
Author(s):  
R Krysiak ◽  
E Obuchowicz ◽  
ZS Herman

The aim of this paper is to review the present knowledge of interactions between the neuropeptide Y (NPY) system and the hypothalamic-pituitary-adrenal (HPA) axis. On the basis of in vitro and in vivo studies of various animal species, we review the effects of NPY on all levels of HPA axis activity. We also describe the effects of glucocorticosteroids on the NPY system in the hypothalamus, including interactions between glucocorticosteroids and insulin. On the basis of available literature, we discuss the role of these interactions in the control of food intake and in the pathogenesis of obesity.


2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Malgorzata Hasiec ◽  
Tomasz Misztal

Both basal and stress-induced secretory activities of the hypothalamic-pituitary-adrenal (HPA) axis are distinctly modified in lactating females. On the one hand, it aims to meet the physiological demands of the mother, and on the other hand, the appropriate and stable plasma cortisol level is one of the essential factors for the proper offspring development. Specific adaptations of HPA axis activity to lactation have been extensively studied in several animal species and humans, providing interesting data on the HPA axis plasticity mechanism. However, most of the data related to this phenomenon are derived from studies in rats. The purpose of this review is to highlight these adaptations, with a particular emphasis on stress reaction and differences that occur between species. Existing data on breastfeeding women are also included in several aspects. Finally, data from the experiments in sheep are presented, indicating a new regulatory factor of the HPA axis—salsolinol—which typical role was revealed in lactation. It is suggested that this dopamine derivative is involved in both maintaining basal and suppressing stress-induced HPA axis activities in lactating dams.


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