scholarly journals Intranasal Administration of Neuropeptide Y Significantly Antagonized Chronic Stress Responses via Central Gabaa Receptors in Male Rats

2021 ◽  
Author(s):  
Yu Yang ◽  
Haijie Yu ◽  
Reji Babygirija ◽  
Bei Shi ◽  
Weinan Sun ◽  
...  
Keyword(s):  
Neuropeptide Y ◽  
Receptor Antagonist ◽  
Mrna Expression ◽  
Hpa Axis ◽  
Stress Responses ◽  
Intranasal Administration ◽  
Male Rats ◽  
Invasive Technique ◽  
Motor Functions ◽  
Colonic Motor

Abstract Stress is widely believed to play a major role in the pathogenesis of many diseases. Central neuropeptide Y (NPY) counteracts the biological actions of corticotropin-releasing factor (CRF), and in turn attenuates stress responses. Administration (intracerebroventricular, ICV) of NPY, significantly antagonized the inhibitory effects of chronic complicated stress (CCS) on gastrointestinal (GI) dysmotility in rats. However, ICV administration is an invasive technique. The effect of intranasal administration of NPY on the hypothalamus-pituitary-adrenal (HPA) axis and GI motility in CCS conditions have not been studied, and the inhibitory mechanism of NPY on CRF through the gamma-aminobutyric acid (GABA)A receptor needs to be further investigated. A CCS rat model was set up, NPY was intranasal administered every day prior to the stress loading. Further, a GABAA receptor antagonist was ICV injected daily. Central CRF and NPY expression were evaluated, serum corticosterone and NPY levels were analyzed, and colonic motor functions was assessed. CCS rats showed significantly increased CRF expression and corticosterone levels, which resulted in enhanced colonic motor functions. Intranasal NPY significantly increased central NPY mRNA expression and reduced central CRF mRNA expression as well as the plasma corticosterone level, helping to restore colonic motor functions. However, ICV administration of the GABAA receptor antagonist significantly abolished these effects. Intranasal administration of NPY upregulates the hypothalamic NPY system. NPY may, through the GABAA receptor, significantly antagonize the overexpressed central CRF and attenuate the HPA axis activities in CCS conditions, exerting influences and helping to restore colonic motor function.

scholarly journals Electro-Acupuncture Attenuates Chronic Stress Responses via Up-Regulated Central NPY and GABAA Receptors in Rats

2021 ◽  
Vol 14 ◽  
Author(s):  
Yu Yang ◽  
Haijie Yu ◽  
Reji Babygirija ◽  
Bei Shi ◽  
Weinan Sun ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Mrna Expression ◽  
Motor Function ◽  
Hpa Axis ◽  
Stress Responses ◽  
Corticosterone Level ◽  
Plasma Corticosterone ◽  
Gamma Aminobutyric Acid ◽  
Motor Functions ◽  
Gastric Motor Function

Stress can increase the release of corticotropin-releasing factor (CRF) in the hypothalamus, resulting in attenuation of gastric motor functions. In contrast, central neuropeptide Y (NPY) can reduce the biological actions of CRF, and in turn weaken stress responses. Although electroacupuncture (EA) at stomach 36 (ST-36) has been shown to have anti-stress effects, its mechanism has not yet been investigated. The effect of EA at ST-36 on the hypothalamus-pituitary-adrenal (HPA) axis and gastrointestinal motility in chronic complicated stress (CCS) conditions have not been studied and the inhibitory mechanism of NPY on CRF through the gamma-aminobutyric acid (GABA)A receptor need to be further investigated. A CCS rat model was set up, EA at ST-36 was applied to the bilateral hind limbs every day prior to the stress loading. Further, a GABAA receptor antagonist was intracerebroventricularly (ICV) injected daily. Central CRF and NPY expression levels were studied, serum corticosterone and NPY concentrations were analyzed, and gastric motor functions were assessed. CCS rats showed significantly elevated CRF expression and corticosterone levels, which resulted in inhibited gastric motor functions. EA at ST-36 significantly increased central NPY mRNA expression and reduced central CRF mRNA expression as well as the plasma corticosterone level, helping to restore gastric motor function. However, ICV administration of the GABAA receptor antagonist significantly abolished these effects. EA at ST-36 upregulates the hypothalamic NPY system. NPY may, through the GABAA receptor, significantly antagonize the overexpressed central CRF and attenuate the HPA axis activities in CCS conditions, exerting influences and helping to restore gastric motor function.

Markers of HPA-axis activity and nucleic acid damage from oxidation after electroconvulsive stimulations in rats

2019 ◽  
Vol 31 (6) ◽  
pp. 287-293
Author(s):  
Anders Jorgensen ◽  
Katrine Breitenstein ◽  
Otto Kalliokoski ◽  
Allan Weimann ◽  
Trine Henriksen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mrna Expression ◽  
Hpa Axis ◽  
Severe Depression ◽  
Male Rats ◽  
Therapeutic Effects ◽  
Middle Aged ◽  
Dna And Rna ◽  
Rna Damage ◽  
Hpa Axis Activity

AbstractObjective:Oxidative stress has been suggested to increase after electroconvulsive therapy (ECT), a treatment which continues to be the most effective for severe depression. Oxidative stress could potentially be mechanistically involved in both the therapeutic effects and side effects of ECT.Methods:We measured sensitive markers of systemic and central nervous system (CNS) oxidative stress on DNA and RNA (urinary 8-oxodG/8-oxoGuo, cerebrospinal fluid 8-oxoGuo, and brain oxoguanine glycosylase mRNA expression) in male rats subjected to electroconvulsive stimulations (ECS), an animal model of ECT. Due to the previous observations that link hypothalamic–pituitary–adrenal (HPA)-axis activity and age to DNA/RNA damage from oxidation, groups of young and middle-aged male animals were included, and markers of HPA-axis activity were measured.Results:ECS induced weight loss, increased corticosterone (only in middle-aged animals), and decreased cerebral glucocorticoid receptor mRNA expression, while largely leaving the markers of systemic and CNS DNA/RNA damage from oxidation unaltered.Conclusion:These results suggest that ECS is not associated with any lasting effects on oxidative stress on nucleic acids neither in young nor middle-aged rats.

scholarly journals Hypoactivity of the Hypothalamo-Pituitary-Adrenocortical Axis during Recovery from Chronic Variable Stress

Endocrinology ◽  
2006 ◽  
Vol 147 (4) ◽  
pp. 2008-2017 ◽  
Author(s):  
Michelle M. Ostrander ◽  
Yvonne M. Ulrich-Lai ◽  
Dennis C. Choi ◽  
Neil M. Richtand ◽  
James P. Herman
Keyword(s):  
Mrna Expression ◽  
Chronic Stress ◽  
Hpa Axis ◽  
Male Rats ◽  
Plasma Acth ◽  
Novel Environment ◽  
Systemic Hypoxia ◽  
Delayed Recovery ◽  
Chronic Variable Stress

Chronic stress induces both functional and structural adaptations within the hypothalamo-pituitary-adrenocortical (HPA) axis, suggestive of long-term alterations in neuroendocrine reactivity to subsequent stressors. We hypothesized that prior chronic stress would produce persistent enhancement of HPA axis reactivity to novel stressors. Adult male rats were exposed to chronic variable stress (CVS) for 1 wk and allowed to recover. Plasma ACTH and corticosterone levels were measured in control or CVS rats exposed to novel psychogenic (novel environment or restraint) or systemic (hypoxia) stressors at 16 h, 4 d, 7 d, or 30 d after CVS cessation. Plasma ACTH and corticosterone responses to psychogenic stressors were attenuated at 4 d (novel environment and restraint) and 7 d (novel environment only) recovery from CVS, whereas hormonal responses to the systemic stressor were largely unaffected by CVS. CRH mRNA expression was up-regulated in the paraventricular nucleus of the hypothalamus (PVN) at 16 h after cessation of CVS, but no other alterations in PVN CRH or arginine vasopressin mRNA expression were observed. Thus, in contrast to our hypothesis, reductions of HPA axis sensitivity to psychogenic stressors manifested at delayed recovery time points after CVS. The capacity of the HPA axis to respond to a systemic stressor appeared largely intact during recovery from CVS. These data suggest that chronic stress selectively targets brain circuits responsible for integration of psychogenic stimuli, resulting in decreased HPA axis responsiveness, possibly mediated in part by transitory alterations in PVN CRH expression.

scholarly journals Urocortin 3 Modulates the Neuroendocrine Stress Response and Is Regulated in Rat Amygdala and Hypothalamus by Stress and Glucocorticoids

Endocrinology ◽  
2006 ◽  
Vol 147 (10) ◽  
pp. 4578-4588 ◽  
Author(s):  
Pauline M. Jamieson ◽  
Chien Li ◽  
Christina Kukura ◽  
Joan Vaughan ◽  
Wylie Vale
Keyword(s):  
Stress Response ◽  
Mrna Expression ◽  
Stress Responses ◽  
Restraint Stress ◽  
Brain Regions ◽  
Lateral Septum ◽  
Male Rats ◽  
Hypothalamic Area ◽  
Selective Ligand ◽  
Urocortin 3

The endogenous corticotropin-releasing factor (CRF) type 2 receptor (CRFR2)-selective ligand urocortin 3 is expressed in discrete subcortical brain regions with fibers distributed mainly to hypothalamic and limbic structures. Close anatomical association between major urocortin 3 terminal fields and CRFR2 in hypothalamus, lateral septum, and medial amygdala (MEA) suggest it is well placed to modulate behavioral and hormonal responses to stress. Urocortin 3 was administered intracerebroventricularly to male rats under basal conditions or before a restraint stress, and circulating ACTH, corticosterone, glucose, and insulin were measured. Urocortin 3 activated the hypothalamic-pituitary-adrenal axis under basal conditions and augmented ACTH responses to restraint stress. Elevated blood glucose with lowered insulin to glucose ratios in both groups suggested increased sympathetic activity. Circulating catecholamines were also increased by urocortin 3, providing additional evidence for sympathoadrenomedullary stimulation. Intracerebroventricular urocortin 3 increased vasopressin mRNA expression in the parvocellular division of the hypothalamic paraventricular nucleus, whereas CRF expression was unchanged, providing a possible mechanism by which urocortin 3 mediates its actions. Urocortin 3 mRNA expression was examined after exposure to stress-related paradigms. Restraint increased levels in MEA with a trend to increased expression in the rostral perifornical hypothalamic area, whereas hemorrhage and food deprivation decreased expression in MEA. Adrenalectomy markedly increased expression in the rostral perifornical hypothalamic area, and high-level corticosterone replacement restored this to control levels. The evidence that urocortin 3 has the potential to influence hormonal components of the stress response and the changes in its expression levels after stressors is consistent with a potential function for the endogenous peptide in modulating stress responses.

Limited cheese intake reduces HPA axis and behavioral stress responses in male rats

2021 ◽  
pp. 113614
Author(s):  
Sarah Fourman ◽  
Dana Buesing ◽  
Sean Girvin ◽  
Houda Nashawi ◽  
Yvonne M. Ulrich-Lai
Keyword(s):  
Hpa Axis ◽  
Stress Responses ◽  
Male Rats ◽  
Behavioral Stress

Differential Effects of CRF1 and CRF2 Receptor Antagonists on Pain-Related Sensitization of Neurons in the Central Nucleus of the Amygdala

2007 ◽  
Vol 97 (6) ◽  
pp. 3893-3904 ◽  
Author(s):  
Guangchen Ji ◽  
Volker Neugebauer
Keyword(s):  
Receptor Antagonist ◽  
Hpa Axis ◽  
Stress Responses ◽  
Background Activity ◽  
Central Nucleus ◽  
Evoked Responses ◽  
Receptor Antagonists ◽  
Peripheral Tissues ◽  
Pain Model ◽  
Crf2 Receptor

As a hormone in the hypothalamic–pituitary–adrenocortical (HPA) axis corticotropin-releasing factor (CRF) mediates stress responses. CRF can also act as a neuromodulator of synaptic transmission outside the HPA axis. A major site of extrahypothalamic expression of CRF and its G-protein–coupled receptors is the amygdala, a key player in affect-related disorders such as anxiety. The laterocapsular division of the central nucleus of the amygdala (CeLC) is important for the modulation of pain affect. This study determined the effects of CRF1 and CRF2 receptor antagonists in CeLC neurons in an arthritis pain model. Extracellular single-unit recordings were made from CeLC neurons in anesthetized adult rats. All neurons responded more strongly to noxious than to innocuous mechanical stimulation (compression) of peripheral tissues, including the knee. Evoked responses and background activity were measured before and during the development of a kaolin/carrageenan-induced knee joint arthritis. Drugs were administered into the CeLC by microdialysis before and/or after arthritis induction. All CeLC neurons showed increased responses to mechanical stimuli (“sensitization”) 5–6 h postinduction of arthritis. A selective CRF1 receptor antagonist ( NBI27914 ; 1–100 μM, concentration in microdialysis probe; 15 min) inhibited evoked responses and background activity in arthritis ( n = 9) but had no effect under normal conditions before arthritis ( n = 9). In contrast, a selective CRF2 receptor antagonist (Astressin-2B; 1–100 μM, 15 min) had no effect in arthritis ( n = 7) but increased the neurons' responses under normal conditions ( n = 8). These data suggest that CRF1 receptors in the amygdala contribute to pain-related sensitization, whereas the normally inhibitory function of CRF2 receptors is lost in the arthritis pain model.

scholarly journals Daily Limited Access to Sweetened Drink Attenuates Hypothalamic-Pituitary-Adrenocortical Axis Stress Responses

Endocrinology ◽  
2007 ◽  
Vol 148 (4) ◽  
pp. 1823-1834 ◽  
Author(s):  
Yvonne M. Ulrich-Lai ◽  
Michelle M. Ostrander ◽  
Ingrid M. Thomas ◽  
Benjamin A. Packard ◽  
Amy R. Furay ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Chronic Stress ◽  
Stress Responses ◽  
Restraint Stress ◽  
Basolateral Amygdala ◽  
Physiological Stress ◽  
Plasma Corticosterone ◽  
Male Rats ◽  
Free Access ◽  
Acute And Chronic Stress

Stress can promote palatable food intake, and consumption of palatable foods may dampen psychological and physiological responses to stress. Here we develop a rat model of daily limited sweetened drink intake to further examine the linkage between consumption of preferred foods and hypothalamic-pituitary-adrenocortical axis responses to acute and chronic stress. Adult male rats with free access to water were given additional twice-daily access to 4 ml sucrose (30%), saccharin (0.1%; a noncaloric sweetener), or water. After 14 d of training, rats readily learned to drink sucrose and saccharin solutions. Half the rats were then given chronic variable stress (CVS) for 14 d immediately after each drink exposure; the remaining rats (nonhandled controls) consumed their appropriate drinking solution at the same time. On the morning after CVS, responses to a novel restraint stress were assessed in all rats. Multiple indices of chronic stress adaptation were effectively altered by CVS. Sucrose consumption decreased the plasma corticosterone response to restraint stress in CVS rats and nonhandled controls; these reductions were less pronounced in rats drinking saccharin. Sucrose or saccharin consumption decreased CRH mRNA expression in the paraventricular nucleus of the hypothalamus. Moreover, sucrose attenuated restraint-induced c-fos mRNA expression in the basolateral amygdala, infralimbic cortex, and claustrum. These data suggest that limited consumption of sweetened drink attenuates hypothalamic-pituitary-adrenocortical axis stress responses, and calories contribute but are not necessary for this effect. Collectively the results support the hypothesis that the intake of palatable substances represents an endogenous mechanism to dampen physiological stress responses.

scholarly journals Direct Evidence that Stimulation of Neuropeptide Y Y5 Receptor Activates Hypothalamo-Pituitary-Adrenal Axis in Conscious Rats via both Corticotropin-Releasing Factor- and Arginine Vasopressin-Dependent Pathway

Endocrinology ◽  
2007 ◽  
Vol 148 (6) ◽  
pp. 2854-2862 ◽  
Author(s):  
Nobukazu Kakui ◽  
Koichi Kitamura
Keyword(s):  
Neuropeptide Y ◽  
Receptor Antagonist ◽  
Hpa Axis ◽  
Arginine Vasopressin ◽  
Combined Treatment ◽  
Previous Treatment ◽  
Corticotropin Releasing Factor ◽  
Receptor Subtype ◽  
Conscious Rats ◽  
Stimulation Of

An abundance of data suggests a crucial role of neuropeptide Y (NPY) as an activator of the hypothamamo-pituitary-adrenal (HPA) axis. However, there is quite limited evidence regarding receptors that mediate this response. Here, we address the possibility that Y5 receptor subtype may be responsible for NPY-induced activation of HPA axis. For this purpose, the effects of an intracerebroventricular injection of Y5-selective agonist, [cPP1–7, NPY19–23, Ala31, Aib32, Gln34]-human pancreatic polypeptide (hPP), on circulating ACTH and corticosterone in conscious rats were evaluated. Central injection of hPP (100 pmol) produced significant increases in plasma ACTH and corticosterone compared with artificial cerebrospinal fluid, and previous treatment with a novel Y5-selective antagonist, FMS586 [3-(9-isopropyl-6,7,8,9-tetrahydro-5H-carbazol-3-yl)-1-methyl-1-(2-pyridin-4-yl-ethyl)-urea hydrochloride] (25 mg/kg, po), completely blocked these alterations. Pretreatment with corticotropin-releasing factor (CRF) receptor antagonist (astressin, 10–50 μg/rat, iv) or arginine vasopressin (AVP) receptor antagonist ([deamino-Pen1, O-Me-Tyr2, Arg8] vasopressin; 3–30 μg/rat, iv) differentially suppressed these increases by 70–80 or 40–50%, respectively. The combined treatment showed no additive effect of these antagonists. Furthermore, an exogenous AVP (0.3 μg/rat, iv)-induced HPA activation was fully inhibited by astressin, suggesting a convergent pathway of AVP receptor signals onto CRF neurons. Central injection of hPP also evoked marked up-regulation of mRNA expression for CRF and AVP in the hypothalamus, which, likewise, were completely reversed by FMS586. Our observations provide the first evidence that selective stimulation of Y5 receptor provokes activation of the HPA axis and its downstream pathway is chiefly composed of both CRF (primary regulator) and AVP (subordinate to the former) with distinct relative contribution.

Sign in / Sign up

Export Citation Format

Share Document