Chronic Stress Rat Model Research Articles

Effects of Chronic Stress on Pancreatic Beta Cell Density in Obese and Lean Zucker Rats

Chronic stress has been implicated as a possible contributing factor to the onset of Type 2 Diabetes Mellitus. PURPOSE:To evaluate beta cell density in a rat model of chronic stress and the metabolic syndrome. METHODS: Obese (OZR) and lean Zucker rats (LZR) were randomly divided into stress (OZR-S, n=4; LZR-S, n=4) and non-stress (OZR-NS, n=4; LZR-NS, n=4) groups. Stress included bath, damp bedding, no bedding, cage tilt, altered light cycles, and cage-switching for 7 hours/day, 5 days/week for 8 weeks, after which animals were euthanized. Pancreases were harvested and flash frozen,7μm thick sections were cut, mounted on glass slides, incubated with an insulin antibody labeled with Alexa-Fluor 546 to identify the beta cells. DAPI was used to label the cell nuclei. Digital images of the pancreas cells were obtained by a Zeiss LSM 510 Confocal microscope using Zenn 2009 software. The insulin positive area was measured using Image J. The images of stained cells and islets were merged and the number of beta cells per islet recorded. A two-way ANOVA was used to compare dependent variables among groups with significance set at P<0.05. RESULTS:There were significant main effects of obesity and stress for all three dependent variables (Table 1). OZR animals had a reduced beta cell density within insulin positive area; however, this was greater in stressed animals. No interactions were observed among groups. CONCLUSIONS:Results indicate that although obesity and metabolic syndrome reduces beta cell density, 8 weeks of chronic stress can overcome this and lead to an increased insulin positive area and greater total beta cell number. The effect of exercise training on these responses are currently under investigation.Table: No title available.

Effects of Dopamine and Serotonin Systems on Modulating Neural Oscillations in Hippocampus-Prefrontal Cortex Pathway in Rats.

Theta and gamma oscillations are believed to play an important role in cognition and memory, and their phase coupling facilitates the information transmission in hippocampal-cortex network. In a rat model of chronic stress, the phase coupling of both theta and gamma oscillations between ventral hippocampal CA1 (vCA1) and medial prefrontal cortex (mPFC) was found to be disrupted, which was associated with the impaired synaptic plasticity in the pathway. However, little was known about the mechanisms underlying the process. In order to address this issue, both dopamine and serotonin as monoaminergic neurotransmitters were involved in this study, since they were crucial factors in pathological basis of depressive disorder. Local field potentials (LFPs) were recorded simultaneously at both vCA1 and mPFC regions under anesthesia, before and after the injection of dopamine D1 receptor antagonist and 5-HT1A receptor agonist, respectively. The results showed that the blockage of D1 receptor could lead to depression-like decrement on theta phase coupling. In addition, the activation of 5-HT1A receptor enhanced vCA1-mPFC coupling on gamma oscillations, and attenuated CA1 theta-fast gamma cross frequency coupling. These data suggest that the theta phase coupling between vCA1 and mPFC may be modulated by dopamine system that is an underlying mechanism of the cognitive dysfunction in depression. Besides, the serotonergic system is probably involved in the regulation of gamma oscillations coupling in vCA1-mPFC network.

Sea buckthorn (Hippophae rhamnoides L.) oil protects against chronic stress-induced inhibitory function of natural killer cells in rats.

Chronic stress can suppress natural killer (NK) cell activity; this may also be related to the effect of stress on the neuroendocrine-immune network. Sea buckthorn (SBT) (Hippophae rhamnoides L.) is a thorny nitrogen fixing deciduous shrub, native to both Europe and Asia. It has been used as a medicinal plant in Tibetan and Mongolian traditional medicines. SBT has multifarious medical properties, including anti-fatigue as well as immunoregulatory effects. This study reports the effects of SBT oil with regard to the cytotoxicity and quantity of NK cells in the blood of a chronic-stress rat model, in addition to its mechanisms on the neuroendocrine-immune network. These results show that SBT oil, given by gavage to rats with chronic stress, could increase the following: body weight, NK cell quantities, and cytotoxicity, as well as the expression of perforin and granzyme B. The results also show that SBT oil in rats with chronic stress could suppress cortisol, ACTH, IL-1β and TNF-α levels, in addition to increasing 5-HT and IFN-γ serum levels. This leads to suggest that SBT oil, in rats with chronic stress, can increase NK cell cytotoxicity by upregulating the expression of perforin and granzyme B, thus causing associated effects of SBT oil on the neuroendocrine-immune network.

Chronic variable stress exposure in male Wistar rats affects the first step of olfactory detection

For most animal species, olfaction plays a paramount role in their perception of the environment. Odours are initially detected in neurons located in the olfactory mucosa. This tissue is regulated by several physiological signals and can be altered in pathology. A number of clinical studies suggest an association between depressive disorders and olfactory sensory loss. In rodents, depressive-like states can be observed in models of chronic stress. We tested the hypothesis that olfactory function might be altered in a rat model of depression, induced by chronic variable stress (CVS). While CVS rats exhibited several symptoms consistent with chronic stress exposure and depressive-like states (increased sucrose intake in sucrose preference test, increased immobility in forced swim test, hyperlocomotion), their odorant responses recorded at the olfactory mucosa level by electro-olfactogram were decreased. In addition we observed increased apoptosis markers in the olfactory mucosa using Western Blot. Our data are consistent with reduced olfactory capacities in a laboratory rat model of chronic stress and depression, in agreement with human clinical data; this warrants further mechanistic studies. Furthermore, this works raises the possibility that altered olfactory function might be a confounding factor in the behavioural testing of chronically stressed or depressed rats.

Brain-Derived Neurotrophic Factor Contributes to Colonic Hypermotility in a Chronic Stress Rat Model.

Brain-derived neurotrophic factor (BDNF) has prokinetic effects on gut motility and is increased in the colonic mucosa of irritable bowel syndrome. We aimed to investigate the possible involvement of BDNF in stress-induced colonic hypermotility. Male Wistar rats were exposed to daily 1-h water avoidance stress (WAS) or sham WAS for 10 consecutive days. The presence of BDNF and substance P (SP) in the colonic mucosa was determined using enzyme immunoassay kits. Immunohistochemistry and western blotting were performed to assess the expression of BDNF and its receptor, TrkB. The contractions of muscle strips were studied in an organ bath system. Repeated WAS increased the fecal pellet expulsion and spontaneous contractile activities of the colonic muscle strips. Both BDNF and SP in the colonic mucosa were elevated following WAS. Immunohistochemistry revealed the presence of BDNF and TrkB in the mucosa and myenteric plexus. BDNF and TrkB were both up-regulated in colon devoid of mucosa and submucosa from the stressed rats compared with the control. BDNF pretreatment caused an enhancement of the SP-induced contraction of the circular muscle (CM) strips. TrkB antibody significantly inhibited the contraction of the colonic muscle strips and attenuated the excitatory effects of SP on contractions of the CM strips. Repeated WAS increased the contractile activities of the CM strips induced by SP after BDNF pretreatment, and this effect was reversed by TrkB antibody. The colonic hypermotility induced by repeated WAS may be associated with the increased expression of endogenous BDNF and TrkB. BDNF may have potential clinical therapeutic use in modulating gut motility.

Insulin-like growth factor 2 mitigates depressive behavior in a rat model of chronic stress

Depression is a common psychiatric disorder associated with chronic stress. Insulin-like growth factor 2 (IGF2) is a growth factor that serves important roles in the brain during development and at adulthood. Here, the role of IGF2 expression in the hippocampus was investigated in a rat model of depression. A chronic restraint stress (CRS) model of depression was established in rats, exhibiting depression-like behavior as assessed with the sucrose preference test (SPT) and forced swimming test (FST), and with evaluation of the corticosterone levels. Hippocampal IGF2 levels were significantly lower in rats suffering CRS than in controls, as were levels of pERK1/2 and GluR1. Lentivirus-mediated hippocampal IGF2 overexpression alleviated depressive behavior in restrained rats, elevated the levels of pERK1/2 and GluR1 proteins, but it did not affect the expression of pGSK3β, GluR2, NMDAR1, and NMDAR2A. These results suggest the chronic restraint stress induces depressive behavior, which may be mediated by ERK-dependent IGF2 signaling, pointing to an antidepressant role for this molecular pathway.

Impairment of Neurovascular Coupling by Chronic Stress

Chronic stress (CS) is a contributory factor in a wide range of diseases. To date, no studies have focused on the effects of chronic stress on neurovascular coupling (NVC). NVC matches neuronal activity with an increase in local blood flow, ensuring that the metabolic demands of the active tissue are satisfied.We studied NVC in a rat model of CS. Rats were exposed to one of 5 stressors each day for 7 days; we have previously shown that this produces an anxious behavioral phenotype. NVC was impaired by CS: vasodilation of parenchymal arterioles evoked by electrical field stimulation in brain slices was greatly reduced, whereas evoked astrocyte endfoot [Ca2+] was enhanced. In isolated amygdalar arterioles of CS rats, dilation evoked by increasing [K+]o was diminished, suggesting an impairment of inward‐rectifier K+ (Kir) channels. In myocytes from CS rats we observed a decrease in Kir current density. Corticosterone delivery produced a similar NVC phenotype to CS, suggesting that this molecule might mediate NVC impairment. These data suggest that CS causes a decrease in Kir channel number in myocytes of amygdalar parenchymal arterioles, possibly through the actions of corticosterone, rendering the vessel less able to respond to small increases in [K+]o released from astrocyte endfeet and resulting in impaired vasodilation after neuronal activity. This impairment may contribute to CNS disorders with a stress component.

Actions of Hydrogen Sulfide and ATP-Sensitive Potassium Channels on Colonic Hypermotility in a Rat Model of Chronic Stress

ObjectiveTo investigate the potential role of hydrogen sulphide (H2S) and ATP-sensitive potassium (KATP) channels in chronic stress-induced colonic hypermotility.MethodsMale Wistar rats were submitted daily to 1 h of water avoidance stress (WAS) or sham WAS (SWAS) for 10 consecutive days. Organ bath recordings, H2S production, immunohistochemistry and western blotting were performed on rat colonic samples to investigate the role of endogenous H2S in repeated WAS-induced hypermotility. Organ bath recordings and western blotting were used to detect the role of KATP channels in repeated WAS.ResultsRepeated WAS increased the number of fecal pellets per hour and the area under the curve of the spontaneous contractions of colonic strips, and decreased the endogenous production of H2S and the expression of H2S-producing enzymes in the colon devoid of mucosa and submucosa. Inhibitors of H2S-producing enzymes increased the contractile activity of colonic strips in the SWAS rats. NaHS concentration-dependently inhibited the spontaneous contractions of the strips and the NaHS IC50 for the WAS rats was significantly lower than that for the SWAS rats. The inhibitory effect of NaHS was significantly reduced by glybenclamide. Repeated WAS treatment resulted in up-regulation of Kir6.1 and SUR2B of KATP channels in the colon devoid of mucosa and submucosa.ConclusionThe colonic hypermotility induced by repeated WAS may be associated with the decreased production of endogenous H2S. The increased expression of the subunits of KATP channels in colonic smooth muscle cells may be a defensive response to repeated WAS. H2S donor may have potential clinical utility in treating chronic stress- induced colonic hypermotility.

Plasma Hormones Facilitated the Hypermotility of the Colon in a Chronic Stress Rat Model

ObjectiveTo study the relationship between brain-gut peptides, gastrointestinal hormones and altered motility in a rat model of repetitive water avoidance stress (WAS), which mimics the irritable bowel syndrome (IBS).MethodsMale Wistar rats were submitted daily to 1-h of water avoidance stress (WAS) or sham WAS (SWAS) for 10 consecutive days. Plasma hormones were determined using Enzyme Immunoassay Kits. Proximal colonic smooth muscle (PCSM) contractions were studied in an organ bath system. PCSM cells were isolated by enzymatic digestion and IKv and IBKca were recorded by the patch-clamp technique.ResultsThe number of fecal pellets during 1 h of acute restraint stress and the plasma hormones levels of substance P (SP), thyrotropin-releasing hormone (TRH), motilin (MTL), and cholecystokinin (CCK) in WAS rats were significantly increased compared with SWAS rats, whereas vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP) and corticotropin releasing hormone (CRH) in WAS rats were not significantly changed and peptide YY (PYY) in WAS rats was significantly decreased. Likewise, the amplitudes of spontaneous contractions of PCSM in WAS rats were significantly increased comparing with SWAS rats. The plasma of WAS rats (100 µl) decreased the amplitude of spontaneous contractions of controls. The IKv and IBKCa of PCSMs were significantly decreased in WAS rats compared with SWAS rats and the plasma of WAS rats (100 µl) increased the amplitude of IKv and IBKCa in normal rats.ConclusionThese results suggest that WAS leads to changes of plasma hormones levels and to disordered myogenic colonic motility in the short term, but that the colon rapidly establishes a new equilibrium to maintain the normal baseline functioning.

Escitalopram Increased Gray Matter and White Matter in a First-Episode Drug-Naïve Panic Disorder Patient Within 6 Weeks

Escitalopram Increased Gray Matter and White Matter in a First-Episode Drug-Naïve Panic Disorder Patient Within 6 Weeks

Neuropeptide Y Reverses Chronic Stress-induced Baroreflex Hypersensitivity in Rats

Chronic stress, as a risk factor for cardiovascular diseases, has been reported to result in elevated plasma neuropeptide Y (NPY) and be highly associated with abnormal cardiac autonomic function. This study aimed to explore the effect of NPY on the chronic stress-induced abnormal baroreceptor reflex sensitivity (BRS). Seven types of recognized stressors were used to develop chronic stress rat model. Subcutaneously implanting ALZET mini-osmotic pumps containing NPY were used to evaluate the action of NPY on the stressed male rats. We found that chronic stress showed no influence on baseline systolic blood pressure (SBP) and heart rate (HR), whereas NPY (85 µg for 30 days) could elevate baseline SBP and induce bradycardia in rats intervened by various stimuli. NPY pretreatment could preserve chronic stress-induced decreases in left ventricular systolic pressure (LVSP) and the maximum rate of change in left ventricular pressure in the isovolumic contraction period (+dp/dt_max) but has shown no effect on left ventricular end diastolic pressure (LVEDP) and the maximum rate of change in left ventricular pressure in the isovolumic relaxation period (-dp/dt_max). Notably, chronic stress led to baroreflex oversensitivity indicated by the elevated ratio of Δheart rate (HR)/ Δmean arterial blood pressure (MABP) in rats followed by vasoconstrictor (phenylephrine, PE) or vasodilator (sodium nitroprusside, SNP) administration, which was almost completely reversed by NPY pretreatment. The expressions of substance P (SP) and gamma aminobutyric acid A receptor (GABA_AR) in nucleus tractus solitarius were increased in chronic stress rats, which were counteracted by NPY pretreatment. We conclude that chronic stress-induced baroreflex hypersensitivity could be blocked by NPY pretreatment. Furthermore, the altered expressions of neurotransmitters and receptors in the brainstem might contribute to this process.

Toll-like receptor 4/nuclear factor-kappa B pathway is involved in myocardial injury in a rat chronic stress model

Chronic stress is considered to predispose to various cardiovascular events such as coronary artery disease, hypertension, and even heart failure. In this study, rats were exposed to stress for 1 day, 1, 2, 3, and 4 weeks to establish a chronic stress model. A specific toll-like receptor 4 (TLR4) antagonist eritoran was used to block the activity of TLR4. On the second day after the last stress exposure, the animals were killed. The expression of TLR4 mRNA and nuclear factor-kappa B (NF-κB) DNA-binding activity in the myocardium were measured using reverse transcriptase polymerase chain reaction and electrophoretic mobility shift assay. The proinflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL-6) in myocardium were assayed by enzyme-linked immunosorbent assay. Myocardial injury was evident after chronic stress for 2 weeks. The TLR4 mRNA expression reached a peak after stress for 1 week. It was sustained at a stable level after stress exposure for 3 weeks and was restored to a nearly normal level in the fourth week. NF-κB DNA-binding activity was significantly enhanced after the stress for 1 day and markedly enhanced again after a 2-week stress exposure. It was weakened and reached a normal level after stress exposure for 4 weeks. The levels of TNF-α and IL-6 gradually increased and reached peaks after stress for 4 weeks. Meanwhile, eritoran significantly decreased the TLR4 mRNA expression and NF-κB activity in rats from the 2-week stress group. However, it did not downregulate the levels of TNF-α and IL-6. Importantly, it significantly improved the myocardial injury induced by the chronic stress. In conclusion, TLR4/NF-κB participates in myocardial injury during chronic stress.

Role of Spinal Microglia in Visceral Hyperalgesia and NK1R Up-Regulation in a Rat Model of Chronic Stress (Gastroenterology 2009;136:1339-1348)

Chronic psychological stress is associated with visceral hyperalgesia. Microglia in the central nervous system are a type of nonneuronal cells and play a key role in the initiation or maintenance of hyperalgesia and allodynia, as demonstrated in animal models of chronic pain caused by peripheral inflammation or nerve injury.1 However, the mechanisms of microglia activation and the downstream pathways leading to amplification of the nociceptive signaling are only partially understood. Activated microglia produce and release a range of proinflammatory mediators, such as cytokines (IL-1, IL-6, tumor necrosis factor α), chemokines, nitric oxide, and prostaglandins, all of which can act on afferent nerve terminals and spinal sensory neurons and increase neuronal excitability.2 The authors wanted to identify the role of spinal microglia in the development of visceral hyperalgesia from chronic stress in a rat model. In the study, the authors used adult male Wistar rats with or without water avoidance (WA) stress. Rats were placed on a block (8×8×10 cm) affixed to the center of a Plexiglas cage (25×25×45 cm) filled with fresh water at room temperature (25℃) to within 1 cm of the top of the block (WA) or kept empty (sham WA) for a period of one hour daily for 10 consecutive days.3 The rats had a surgically implanted chronic intrathecal (IT) catheter and an osmotic mini-pump. The rats then had a Teflon-coated electrode inserted into the external oblique musculature for electromyographic (EMG) recording.4 One group of rats was exposed to chronic WA stress or sham WA for 10 days and were sacrificed on day 11. Samples of lumbar spinal cord (L6S1) were collected and processed for immunohistochemically for P-p38, the microglia marker OX42, or the neuronal marker NeuN. Also, other groups of rats were exposed to WA stress or sham stress for 10 days and given daily injections of minocycline, the mitogen-activated protein kinase (MAPK) p38 inhibitor SB203580, or vehicle (0.9% saline) via osmotic pump connected to an IT catheter. Phosphorylation levels of the kinase p38 (P-p38), the microglia marker OX42, NK1R, and IκBα were assessed by immunoblotting and/or immunostaining of spinal samples. The authors also performed EMG recordings and baseline recordings of the visceromotor response (VMR) to colorectal distention (CRD) before beginning the treatment (day 0) and then again 24 hours after the last WA or sham WA sessions (day 11). The effects of the microglia-activating factor fractalkine were assessed on the visceral sensitivity in control nonstressed rats exposed to minocycline or vehicle. The immunohistochemistry for the activation marker of microglia, P-p38, revealed greater P-p38 staining in the spinal dorsal horn from WA stressed rats compared with controls. The immunoreactivity for P-p38 colocalized with OX42-positive cells (microglia) from WA stressed rats. Western blotting also demonstrated increased levels of P-p38 in WA stressed rats compared with controls. This increase was inhibited by treatment with IT minocycline or with IT SB203580. Western blotting showed increased expression of NK1R in WA stressed rats compared with controls. Stress-induced increased NK1R expression was completely blocked by minocycline but not SB203580. WA stress induced decreased IκBα expression, and this decrease was partially blocked by minocycline and SB203580. WA stress induced hyperalgesia in stressed rats treated with vehicle. WA induced visceral hyperalgesia was blocked by daily treatment with IT injection of minocycline or SB203580. Fractalkine injection-induced hyperalgesia was blocked by minocycline.

Effects of escitalopram on the regulation of brain‐derived neurotrophic factor and nerve growth factor protein levels in a rat model of chronic stress

Escitalopram (ES-CIT) is a widely used, highly specific antidepressant. Until now there has been very little evidence on how this drug under pathological conditions affects an important feature within the pathophysiology of stress-related disorders such as depression: the endogenous neurotrophins. By using a well-characterized rat model in which chronic stress induces depressive-like behavior, the levels of neurotrophins brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were determined in representative brain regions and serum using a highly sensitive improved fluorometric two-site ELISA system. There was a significant increase of BDNF in the left and right cortices after stress treatment (twofold increase) that was reversed by application of ES-CIT. An ES-CIT-dependent NGF reduction in stressed rats was detectable in the right cortex only (P = 0.027). The left hippocampus revealed significantly higher amounts of BDNF (2.5-fold increase) protein than the right hippocampus. These interhemispheric differences were unrelated to stress or ES-CIT treatment in all animals. BDNF and NGF of the frontal cortex, cerebellum, and serum did not change between the study groups. There was a negative correlation between body weight and serum BDNF, independent of stress or ES-CIT treatment. In conclusion, BDNF and NGF show substantial changes in this rodent model of chronic social stress, which is susceptible to antidepressant treatment with ES-CIT and therefore may constitute a neurobiological correlate for the disease.

Adaptogenic effect of Morus alba on chronic footshock-induced stress in rats

Objective:The objective of the present study was to evaluate the adaptogenic property of the ethyl acetate-soluble fraction of methanol extract of Morus alba roots against a rat model of chronic stress (CS).Materials and Methods:Rats were exposed to stress procedure for 21 days. The stress procedure was mild, unpredictable footshock, administered for 1 h once daily for 21 days. Rats were administered with the ethyl acetate soluble fraction of methanol extract of M. alba roots (25, 50 and 100 mg/kg p.o) 1 h before footshock for 21 days and behavioral parameters were evaluated for cognitive dysfunction and depression using elevated plus maze and despair swim test, respectively. On day 21, rats were sacrificed immediately after stress and blood was collected for biochemical estimation. The adrenal gland and spleen were dissected for organ weight and the stomach was dissected for ulcer score.Results:CS significantly induced cognitive deficit, mental depression and hyperglycemia and increased blood corticosterone levels, gastric ulcerations and adrenal gland weight, but decreased the splenic weight. Pre-treatments with the ethyl acetate soluble fraction of methanol extract of M. alba roots (25, 50 and 100 mg/kg, p.o.) significantly attenuated the CS-induced perturbations. Diazepam (1 mg/kg, p.o.) was used as the standard antistress drug.Conclusion:The results indicate that M. alba possesses significant adaptogenic activity, indicating its possible clinical utility as an antistress agent.

Role of Spinal Microglia in Visceral Hyperalgesia and NK1R Up-Regulation in a Rat Model of Chronic Stress

Chronic psychological stress is associated with visceral hyperalgesia and increased expression of spinal NK1 receptors (NK1Rs). We aimed to identify the role of spinal microglia in this process. Male Wistar rats were exposed to water avoidance (WA) or sham stress 1 hour each day for 10 days and given daily injections of minocycline, the p38 inhibitor SB203580, or saline. Phosphorylation levels of the kinase p38 (P-p38), the microglia marker OX42, NK1R, and IkappaBalpha were assessed by immunoblotting and/or immunostaining of spinal samples collected at day 11. The visceromotor response to colorectal distention at baseline and following WA were also assayed in rats given injections of minocycline, SB203580, or vehicle. The effects of fractalkine were assessed on the visceromotor response in rats exposed to minocycline or vehicle. P-p38 protein levels and immunoreactivity were increased in stressed rats and colocalized with OX42-positive cells and neurons in the dorsal horn. This increase was reversed by minocycline or SB203580 exposure. Stress-induced increased NK1R expression was blocked by minocycline but not SB203580. WA-induced decreased IkappaBalpha expression was blocked by minocycline and SB203580. WA-induced hyperalgesia was blocked by minocycline and SB203580 intrathecally. Fractalkine-induced hyperalgesia was blocked by minocycline. This is the first demonstration that stress-induced activation of spinal microglia has a key role in visceral hyperalgesia and associated spinal NK1R up-regulation.

T1450 Glucocorticoids Mediate Spinal Microglia Activation and Visceral Hyperalgesia in a Rat Model of Chronic Stress

T1450 Glucocorticoids Mediate Spinal Microglia Activation and Visceral Hyperalgesia in a Rat Model of Chronic Stress

The effects of electroacupuncture on open-field behavior and recognitive function of the chronic stress model rats

目的 观察电针与氟西汀对大鼠抑郁行为和认知功能的影响,探讨其作用的不同机制.方法 采用孤养结合慢性温和应激大鼠模型,对不同组大鼠进行电针与氟西汀干预.以体质量为指标进行大鼠一般状况评价;运用开场实验评定大鼠行为改变;运用Morris水迷宫成绩评定大鼠认知功能改变.结果 21 d后,正常组、模型组、电针组和氟西汀组水平运动次数分别为(24.1±7.05) 次、(10.1±4.6) 次、(17.3±8.21) 次、(11.8±4.13) 次,其中模型组、氟西汀组与正常组比较差异有极显著性(P ＜0.01),电针组与正常组比较差异有显著性(P ＜0.05);各组间垂直运动差异无显著性(P ＞0.05);正常组、模型组、电针组和氟西汀组Morris水迷宫潜伏期分别为(10.46±2.57)s、(30.27±3.56)s、(21.16±4.86)s、(17.76±5.78)s,其中模型组、电针组、氟西汀组与正常组相比均显著增加(P ＜0.01),电针组、氟西汀组与模型组相比持续时间下降差异有极显著性(P ＜0.01).结论 电针与氟西汀皆可减轻慢性应激模型大鼠体质量下降,改善其行为与认知功能抑制,但二者作用各有优势,提示其机制可能不同。

Adaptogenic activity of Withania somnifera: an experimental study using a rat model of chronic stress

Withania somnifera (WS) Dunal is classified in Ayurveda, the ancient Hindu system of medicine, as a rasayana, a group of plant-derived drugs reputed to promote physical and mental health, augment resistance of the body against disease and diverse adverse environmental factors, revitalise the body in debilitated conditions and increase longevity. These attributes are remarkably similar to the properties ascribed to adaptogens like Panax ginseng (PG) in contemporary medicine. As such, the adaptogenic activity of a standardised extract of WS roots was investigated against a rat model of chronic stress (CS). The stress procedure was mild, unpredictable footshock, administered once daily for 21 days to adult male Wistar rats. CS induced significant hyperglycaemia, glucose intolerance, increase in plasma corticosterone levels, gastric ulcerations, male sexual dysfunction, cognitive deficits, immunosuppression and mental depression. These CS induced perturbations were attenuated by WS (25 and 50 mg/kg po) and by PG (100 mg/kg po), administered 1 h before footshock for 21 days. The results indicate that WS, like PG, has significant antistress adaptogenic activity, confirming the clinical use of the plant in Ayurveda.

Altered regulation of gene and protein expression of hypothalamic-pituitary-adrenal axis components in an immature rat model of chronic stress.

Chronic stress early in postnatal life influences hormonal and behavioural responses to stress persistently, but the mechanisms and molecular cascades that are involved in this process have not been clarified. To approach these issues, a chronic stress paradigm for the neonatal rat, using limited bedding material to alter the cage environment, was devised. In 9-day-old rats subjected to this chronic stress for 1 week, significant and striking changes in the expression and release patterns of key molecules that govern the neuroendocrine stress responses were observed. The presence of sustained stress was evident from enhanced activation of peripheral elements of the neuroendocrine stress response, i.e. increased basal plasma corticosterone concentrations, high adrenal weight and decreased body weight. Central regulatory elements of the neuroendocrine stress response were perturbed, including reduced expression of hypothalamic corticotropin-releasing hormone that, surprisingly, was accompanied by reduced glucocorticoid receptor expression. Thus, the effects of chronic sustained stress in the neonatal rat on the hypothalamic-pituitary-adrenal axis included substantial changes in the expression and activity of major regulators of this axis. Importantly, the changes induced by this chronic stress differed substantially from those related to acute or recurrent stress, providing a novel model for studying the long-term effects of chronic, early life stress on neuroendocrine functions throughout life.