Cold Water Swim Research Articles

Cold water swimming and upper respiratory tract infections

It is often suggested that habitual cold water swimming (HCS) may improve resistance to infection [1], yet research into effects of HCS on the immune system has produced inconclusive results. This may be due to the wide range of protocols, from brief ice-cold dips [2] to long cold water swims [3]. Many studies measured blood and saliva markers rather than actual illness, and the clinical significance of these markers is not well established [4]. Incidence of upper respiratory tract infection (URTI), i.e. the common cold, is a useful indication of in vivo immune system function [5,6]. This study compared URTI susceptibility in those practising HCS with that in their non-swimming co-habiting partners. To control for any effect of swimming, those who swim in indoor heated pools and their partners were also investigated. The null hypothesis (H0) was that there would be no difference between swimming groups.

Enhanced functional recovery from sciatic nerve crush injury through a combined treatment of cold-water swimming and mesenchymal stem cell transplantation

Objective:Although regimens of stem cell implantation can elicit functional recovery following peripheral nerve injury, the degree of outcome is still limited. This study evaluated the synergistic effects of cold-water swimming (CWS) and mesenchymal stem cell (MSC) transplantation on functional recovery of crushed sciatic nerve in rats.Method:Forty Sprague-Dawley rats that had their sciatic nerve crushed during surgery were randomly divided into four groups: MSCCWS group, treated with combination of MSC and CWS; MSC group, treated with MSC alone; CWS group, treated with CWS alone; and non-treated group, without any treatments. The sciatic function index (SFI), vertical activity (VA), ankle activity (AA) and electrophysiological study were examined before, immediately after surgery, after the treatment and after 4 weeks from treatment. Morphological and S100 immunohistochemical studies were also performed.Results:The MSCCWS group showed a greater improvement in SFI, VA, AA, peak amplitudes and onset latencies of compound muscle action potential (CMAP) in sciatic nerve and infiltration of immune cells with significant difference from the MSC, CWS and non-treated groups (P < 0.05).Conclusions:MSC transplantation combined with CWS could achieve better results in functional recovery than a single treatment of MSC alone or CWS alone in nerve crush injury.

Adaptation of the Cold Shock Response and Cooling Rates on Swimming Following Repeated Cold Water Immersions in a Group of Children Aged 10 – 12 years

Habituation of the cold shock response and adaptation in deep body cooling with prolonged cold water immersion is well documented in adults. This study aimed to determine whether children exhibit similar adaptive responses. Eight children aged 10–11 years underwent a 5 min static immersion in 15 °C (59 °F) water, five then swam for up to 40 min, before and after a year of regular cold water swim training. Following acclimatization, no differences were found in heart rates or respiratory frequencies on initial immersion, despite a smaller relative VO2. Children reported feeling warmer (p < .01) and more comfortable (p < .05), implying acclimatization of subjective perception of cold. No difference was found in cooling rates while swimming. On comparison with data of adults swimming in 12 °C (53.6 °F) water, no difference was found in cooling rates, but the trend in both acclimatized groups to a slower rate of cooling was significant (p ≤ .026) when the data were pooled. These data may support a theory of insulative adaptation.

The critical role of spinal 5-HT7 receptors in opioid and non-opioid type stress-induced analgesia

The opioid and non-opioid types of stress-induced analgesia have been well defined. One of the non-opioid type involve the endocannabinoid system. We previously reported that the spinal serotonin 7 receptor (5-HT7) blockers inhibit both morphine and cannabinoid-induced analgesia, thus we hypothesized that descending serotonergic pathways-spinal 5-HT7 receptor loop might contribute to stress-induced analgesia.Stress-induced analgesia was induced with warm (32°C) or cold (20°C) water swim stress in male Balb-C mice. The effects of intrathecal injection of a selective 5-HT7 receptor antagonist, SB 269970, of the denervation of serotonergic neurons by intrathecal administration of 5,7-dihydroxytryptamine (5,7-DHT) and of lesions of the dorsolateral funiculus on opioid and non-opioid type stress-induced analgesia were evaluated with the tail-flick and hot plate tests. The expression of 5-HT7 receptors mRNA in the dorsal lumbar region of spinal cord were analyzed by RT-PCR following spinal serotonin depletion or dorsolateral funiculus lesion. The effects of the selective 5-HT7 receptor agonists LP 44 and AS 19 were tested on nociception.Intrathecal SB 269970 blocked both opioid and non-opioid type stress-induced analgesia. Dorsolateral funiculus lesion or denervation of the spinal serotonergic neurons resulted in a marked decrease in 5-HT7 receptor expression in the dorsal lumbar spinal cord, accompanied by inhibition of opioid and non-opioid type stress-induced analgesia. However, the systemic or intrathecal LP 44 and AS 19 alone did not produce analgesia in unstressed mice.These results indicate that descending serotonergic pathways and the spinal 5-HT7 receptor loop play a crucial role in mediating both opioid and non-opioid type stress-induced analgesia.

Effect of bacopa monniera on cold stress induced neurodegeneration in hippocampus of wistar rats: a histomorphometric study.

Bacopa monniera/ Brahmi,is used over centuries in Ayurvedic medicine for memory development, learning, concentration and other mental illnesses such as nervousness and poor cognition. The present study aims to evaluate the effect of Bacopa monniera (Brahmi, BM) on cold stress induced histological changes in hippocampus of Wistar rats. Total 24 male rats divided into four groups were used (n=6) for this study. Group I was control in which rats were kept under ideal laboratory conditions, Group II was given 40 mg/kg of BM extract, Group III was cold water swim stress in which rats were forced to swim in the cold water maintained at 18±2(o)C till it started to sink for a period of one month and Group IV in which cold water swim stress given for a month followed by oral administration of BM extracts 40mg/kg treatment for a month. The whole study was carried out for a period of 60 d. The animals were sacrificed next day and their brains dissected out for histomorphometric analysis. The diameter, packing density and total number of neurons were calculated from stained histological section by using micrometry in the CA-1 region of the hippocampus. The analysis and plotting of graphs were carried out using Sigma Plot 12 (Systat Software Inc., USA). Values are expressed as Mean ± SEM (n = 6). One way analysis of variance followed by Student-Newman-Keul's multiple comparisons test was used for the comparison of means. A probability of 0.05 and less was taken as statistically significant. The results showed that there is no significant difference in the diameter of the cells between the groups but total number of the cells in Group II was statistically significant when compared with the others groups. Student-Newman-Keuls method showed that Group II and Group IV are statistically significant when compared to Group III (p<0.05). RESULTS indicates that when BM extracts administered orally produce neuroprotective effect in cold stress induced hippocampal neurodegeneration of rats. Hence, the herb BM can possibly be used as an adjuvant to improve memory to combat stress in our day to day life.

Effects of Lycium barbarum polysaccharides on oxidative stress in hyperlipidemic mice following chronic composite psychological stress intervention.

Chronic composite psychological stress intervention is the accumulation of factors which may induce psychological stress, including food deprivation, water deprivation and swimming in cold water. Approximately 40% of cases of atherosclerosis are associated with chronic composite psychological stress. The aim of the present study was to explore the effects of Lycium barbarum polysaccharides (LBP) on blood lipid levels and oxidative stress in hyperlipidemic mice, following chronic composite psychological stress. A hyperlipidemic mouse model was generated, and the mice were subjected to chronic composite psychological stress and treated with LBP for 30 days. After 30 days the triglyceride (TG) and total cholesterol (TC) levels were measured in the serum, and the mRNA expression levels of cholesterol 7α‑hydroxylase (CYP7A1) were determined in the liver, in order to observe any changes to lipid metabolism. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were measured in the liver to evaluate the effects of LBP on oxidative stress. The blood serum levels of interleukin‑6 (IL‑6) and heat shock protein 70 (HSP‑70) were measured to evaluate the extent of the aortic inflammatory response, and to determine the protective effects of LBP. The levels of TG, TC, MDA and IL‑6 were significantly higher in the mice subjected to chronic composite psychological stress (HS), as compared with the mice treated with LBP alone (HL), or treated with LBP and subjected to stress (HLS). In addition, SOD and HSP‑70 levels, and the mRNA expression levels of CYP7A1 were significantly lower in the HS group, as compared with that in the HL and HLS groups. These results suggest that chronic composite psychological stress may promote the occurrence and development of atherosclerosis, by inducing the aortic inflammatory response and lipid peroxidation. Furthermore, treatment with LBP significantly inhibited oxidative stress and the aortic inflammatory response.

How Does Stress-Induced Activation of the Kappa Opioid System Increase Addiction Risk?

How Does Stress-Induced Activation of the Kappa Opioid System Increase Addiction Risk?

Spermatogenesis Process Following Chronic Swimming and Standing in Cold, Warm and Lukewarm Water

Background: Physical activity and alteration of temperature as a source of stress may have adverse effects on male reproduction. Objectives: The aim of this study was to investigate the effect of chronic swimming and standing in cold, warm and lukewarm water on mouse spermatogenesis. Materials and Methods: Forty-nine male mice (N = 49) were randomly divided into seven groups: C, control; SwC, swimming in cold water (10°C); StC, standing in cold water (10°C); SwL, swimming in lukewarm water (23°C); StL, standing in lukewarm water (23°C); SwW, swimming in warm water (36°C); StW, standing in warm water (36°C). Animals in swimming groups were submitted to daily forced swimming for five minutes for five consecutive days/week during five weeks. However groups StC, StL and StW were only standing on a raised platform inside the water pool, without swimming, for the same time and duration. Evaluations on day 36 were made using enzyme linked immunosorbent assay (ELISA), Johnsen score and immunohistochemistry for assay of serum testosterone, luteinizing hormone (LH) levels, quality of spermatogenesis and detection of apoptosis, respectively. Results: Serum LH and testosterone levels as well as Johnsen score were significantly reduced in all groups except for the group standing in lukewarm water (P < 0.05). Apoptosis was increased only in the swimming or standing in warm water groups (P < 0.05). Conclusions: This study indicates that forced swimming and standing in all water temperatures has adverse effects on male fertility parameters, the only exception is standing in lukewarm water, which seems to be safe for male fertility parameters.

Proteomic analysis on infantile spasm and prenatal stress

Infantile spasms (IS) are an age-dependent epileptic encephalopathy with severe cognitive dysfunction. Prenatal stress (PS) has been reported to increase the risk for IS through clinical and animal studies. We aim to investigate the mechanism of brain damage caused by IS and the effect of PS. Animals were divided into 4 groups: PS-spasm model, PS-saline control, NS-spasm model, and saline control. N-methyl-d-aspartate (NMDA) was used to induce spasm and swimming in cold water was used to induce PS. A proteomics-based approach was used to compare the NS-spasm model vs. saline control, and PS-spasm model vs. NS-spasm model. Gel image analysis was followed by mass spectrometric protein identification and bioinformatics analysis. We observed an increased spasm frequency (t=8.65, P<0.001), and a shorter latency period (t=3.96, P<0.001) in the PS-spasm model vs. the NS-spasm model. In the NS-spasm model vs. saline control, the main differentially expressed proteins were CFL1, PKM2, PRPS2, DLAT, CKB, DPYSL3, and SNAP25. In the PS-spasm model vs. NS-spasm model, MDH1 and YWHAZ were differentially expressed. YWHAZ was directly connected with CFL1 in protein networks. YWHAZ and CFL1 were further validated by Western blot analysis. The biological function of differentially expressed proteins indicates the pathogenesis of IS maybe relevant to energy metabolism, brain development, and neural remodeling. PS aggravated seizures in the NMDA-induced spasm model, YWHAZ, and CFL1 may be involved.

Moving in extreme environments: open water swimming in cold and warm water.

Open water swimming (OWS), either ‘wild’ such as river swimming or competitive, is a fast growing pastime as well as a part of events such as triathlons. Little evidence is available on which to base high and low water temperature limits. Also, due to factors such as acclimatisation, which disassociates thermal sensation and comfort from thermal state, individuals cannot be left to monitor their own physical condition during swims. Deaths have occurred during OWS; these have been due to not only thermal responses but also cardiac problems. This paper, which is part of a series on ‘Moving in Extreme Environments’, briefly reviews current understanding in pertinent topics associated with OWS. Guidelines are presented for the organisation of open water events to minimise risk, and it is concluded that more information on the responses to immersion in cold and warm water, the causes of the individual variation in these responses and the precursors to the cardiac events that appear to be the primary cause of death in OWS events will help make this enjoyable sport even safer.

Poststress Block of Kappa Opioid Receptors Rescues Long-Term Potentiation of Inhibitory Synapses and Prevents Reinstatement of Cocaine Seeking

Dopaminergic neurons in the ventral tegmental area of the brain are an important site of convergence of drugs and stress. We previously identified a form of long-term potentiation of gamma-aminobutyric acid (GABA)ergic synapses on these neurons (LTPGABA). Our studies have shown that exposure to acute stress blocks this LTP and that reversal of the block of LTPGABA is correlated with prevention of stress-induced reinstatement of cocaine-seeking behavior. Sprague-Dawley rats were subjected to cold-water swim stress. Midbrain slices were prepared following stress, and whole-cell patch clamp recordings of inhibitory postsynaptic currents were performed from ventral tegmental area dopamine neurons. Antagonists of glucocorticoid receptors and kappa opioid receptors (κORs) were administered at varying time points after stress. Additionally, the ability of a kappa antagonist administered following stress to block forced swim stress-induced reinstatement of cocaine self-administration was tested. We found that an acute stressor blocks LTPGABA for 5 days after stress through a transient activation of glucocorticoid receptors and more lasting contribution of κORs. Even pharmacological block of κORs beginning 4 days after stress has occurred reversed the block of LTPGABA. Administration of a κORs antagonist following stress prevents reinstatement of cocaine-seeking behavior. A brief stressor produces changes in the reward circuitry lasting several days. Our findings reveal roles for glucocorticoid receptors and κORs as mediators of the lasting effects of stress on synaptic plasticity. κORs antagonists reverse the neuroadaptations underlying stress-induced drug-seeking behavior and may be useful in the treatment of cocaine addiction.

Cold water forced swimming stress induced metabolic alterations in rats

Forced swimming in cold water causes physiological and psychological stress that leads to altered biochemical homeostasis and neurobehavioral responses. In this study, plasma and urinary metabolites in Sprague-Dawley (SD) rats subjected to cold water forced swimming stress (CWFSS) were characterized using NMR in conjunction with multivariate data analysis. Metabolic analysis demonstrated that decreased levels of lipoprotein and increased levels of O-acetyl glycoprotein, glucose, lactate, pyruvate, creatine, citrate, succinate and amino acids including phenylalanine, tyrosine, glutamate, valine, isoleucine, alanine and lysine in plasma were observed in response to CWFSS. Moreover, the biochemical response to CWFSS as determined from NMR analysis of urine was characterized by an elevation of gut microbiota-related metabolites including phenylacetylglycine, 4-cresol glucuronide and indoxyl sulfate. These results suggest that CWFSS-induced metabolic perturbations were involved in the disruption of amino acid and energy metabolism as well as the alteration of gut microbiota function. This study will enhance the current knowledge of stress-induced diseases and aid in the early diagnosis of metabolic disorders in humans.

Therapeutic effect of bone marrow mesenchymal stem cells on cold stress induced changes in the hippocampus of rats.

The present study aims to evaluate the effect of bone marrow mesenchymal stem cells on cold stress induced neuronal changes in hippocampal CA1 region of Wistar rats. Bone marrow mesenchymal stem cells were isolated from a 6-week-old Wistar rat. Bone marrow from adult femora and tibia was collected and mesenchymal stem cells were cultured in minimal essential medium containing 10% heat-inactivated fetal bovine serum and were sub-cultured. Passage 3 cells were analyzed by flow cytometry for positive expression of CD44 and CD90 and negative expression of CD45. Once CD44 and CD90 positive expression was achieved, the cells were cultured again to 90% confluence for later experiments. Twenty-four rats aged 8 weeks old were randomly and evenly divided into normal control, cold water swim stress (cold stress), cold stress + PBS (intravenous infusion), and cold stress + bone marrow mesenchymal stem cells (1 × 106; intravenous infusion) groups. The total period of study was 60 days which included 1 month stress period followed by 1 month treatment. Behavioral functional test was performed during the entire study period. After treatment, rats were sacrificed for histological studies. Treatment with bone marrow mesenchymal stem cells significantly increased the number of neuronal cells in hippocampal CA1 region. Adult bone marrow mesenchymal stem cells injected by intravenous administration show potential therapeutic effects in cognitive decline associated with stress-related lesions.

The effects of lactational maternal stress on neuronal behavior of adolescent offspring in mice

Objective To explore the effects of lactational maternal stress on neurobehavioral development of offsprings. Methods Maternal mice were divided into normal control, maternal deprivation and maternal stress group. A 5-min/day cold water swimming was used as maternal stress for continuously of 14 day since the 7th postnatal day. The increasing bodyweight and neurobehavior of adolescent offspring mice were assessed by forced swimming test, tail suspension test and locomotor activity in the 35th postnatal day. Results Maternal chronic stress in lactational stage significantly increased the vulnerability of offspring to acute stress, which was reflected by significantly increased immobility time of adolescent offspring in forced swimming test(female: (139±6)s, (138±9)s, (96±9)s respectively; male: (139±9)s, (112±9)s, (96±9)s respectively) and in tail suspension test(femal: (127±8)s, (123±8)s, (98±6)s respectively; male: (141±7)s, (105±5)s, (92±6)s respectively). Meanwhile, sexual difference occurred for adolescent offspring to acute stress, and the female offspring were more vulnerable to acute stress. Conclusion Lactational maternal stress may be important factors for development of adolescent depression.Our findings highlight the area of early prevention and intervention for adolescent depression . Key words: Maternal stress; Lactation; Neuronal behavior; Adolescent depression

Intermittent swim stress causes Morris water maze performance deficits in a massed-learning trial procedure that are exacerbated by reboxetine

Various animal models of depression have been used to seek a greater understanding of stress-related disorders. However, there is still a great need for research in this area, as many unanswered questions remain. Therefore, we sought to employ a novel animal model of depression known as intermittent swim stress (ISS). In this model, the animal experiences 100 trials of cold water swim stress. ISS has already shown subsequent immobility in the forced swim test (FST), deficits in instrumental and spatial (spaced-trial procedure), and responsiveness to norepinephrine. We are now examining how this will translate in the Morris water maze for rats in a massed-learning trial procedure, and further assessing ISS sensitivity toward norepinephrine selective anti-depressant drugs. The results indicated no difference in cued learning when the platform was visible in the water maze, but a hidden platform task revealed poorer spatial learning for ISS-exposed rats versus controls. In terms of spatial memory, there was a notable ISS-induced deficit 1h after the learning trials, regardless of performance on the previous platform task. Interestingly, the administration of reboxetine interfered with the spatial learning and memory trials for both ISS and CC groups. As a result, ISS exposure compromised spatial learning and memory in the Morris water maze, and norepinephrine does not appear to be a mediator of this deficit. The results demonstrate a key difference in the effects of reboxetine in a massed- vs. spaced-learning trial procedure in the Morris water maze following ISS exposure.

Prior cold water swim stress alters immobility in the forced swim test and associated activation of serotonergic neurons in the rat dorsal raphe nucleus

Prior adverse experience alters behavioral responses to subsequent stressors. For example, exposure to a brief swim increases immobility in a subsequent swim test 24h later. In order to determine if qualitative differences (e.g. 19°C versus 25°C) in an initial stressor (15-min swim) impact behavioral, physiological, and associated neural responses in a 5-min, 25°C swim test 24h later, rats were surgically implanted with biotelemetry devices 1week prior to experimentation then randomly assigned to one of six conditions (Day 1 (15min)/Day 2 (5min)): (1) home cage (HC)/HC, (2) HC/25°C swim, (3) 19°C swim/HC, (4) 19°C swim/25°C swim, (5) 25°C swim/HC, (6) 25°C swim/25°C swim. Core body temperature (Tb) was measured on Days 1 and 2 using biotelemetry; behavior was measured on Day 2. Rats were transcardially perfused with fixative 2h following the onset of the swim on Day 2 for analysis of c-Fos expression in midbrain serotonergic neurons. Cold water (19°C) swim on Day 1 reduced Tb, compared to both 25°C swim and HC groups on Day 1, and, relative to rats exposed to HC conditions on Day 1, reduced the hypothermic response to the 25°C swim on Day 2. The 19°C swim on Day 1, relative to HC exposure on Day 1, increased immobility during the 5-min swim on Day 2. Also, 19°C swim, relative to HC conditions, on Day 1 reduced swim (25°C)-induced increases in c-Fos expression in serotonergic neurons within the dorsal and interfascicular parts of the dorsal raphe nucleus. These results suggest that exposure to a 5-min 19°C cold water swim, but not exposure to a 5-min 25°C swim alters physiological, behavioral and serotonergic responses to a subsequent stressor.

Sex differences associated with intermittent swim stress

Various animal models of depression have been used to seek a greater understanding of stress-related disorders. However, there is still a great need for novel research in this area, as many individuals suffering from depression are resistant to current treatment methods. Women have a higher rate of depression, highlighting the need to investigate mechanisms of sex differences. Therefore, we employed a new animal model to assess symptoms of depression, known as intermittent swim stress (ISS). In this model, the animal experiences 100 trials of cold water swim stress. ISS has already been shown to cause signs of behavioral depression in males, but has yet to be assessed in females. Following ISS exposure, we looked at sex differences in the Morris water maze and forced swim test. The results indicated a spatial learning effect only in the hidden platform task between male and female controls, and stressed and control males. A consistent spatial memory effect was only seen for males exposed to ISS. In the forced swim test, both sexes exposed to ISS exhibited greater immobility, and the same males and females also showed attenuated climbing and swimming, respectively. The sex differences could be due to different neural substrates for males and females. The goal of this study was to provide the first behavioral examination of sex differences following ISS exposure, so the stage of estrous cycle was not assessed for the females. This is a necessary future direction for subsequent experiments. The current article highlights the importance of sex differences in response to stress.

Study on evaluation system for gynecological disease model characterized by Qi stagnation and blood stasis syndrome with female SD rats

To establish an evaluation system for animal model with gynecological disease characterized by Qi stagnation and blood stasis syndrome, in order to disprove syndrome characteristics of the model by classic clinical prescriptions, and evaluate the specificity and reliability of the model with macroscopic biological signs and symptoms. The model characterized by Qi stagnation and blood stasis syndrome was established by injecting adrenaline into female SD rats and conducting unpredictable chronic stimulus such as reversal of day and night, swimming in cold water, thermal stimulation in oven, noise and tail suspension for two weeks. They were also orally administered with Xiangfu Siwu Tang, Shaofu Zhuyu Tang and positive control drug aspirin in groups. A comprehensive evaluation was conducted for the model on the basis of haemorheology, four blood coagulation indexes, four diagnostic information (digital imaging of tongue, paw and tail, temperature, weight, ingestion, electrocardiograph, and open filed test), and syndrome rating. Compared with the normal group, the model group showed obvious changes in haemorheology, four blood coagulation indexes, animal behavior, weight, ingestion, syndrome rating and heart rate. Their tongue and paw pictures were analyzed with Photoshop 7.0, showing significant difference in red, green and blue percentage composition from the normal group. Groups given aspirin and Xiangfu Siwu Tang showed notable changes in haemorheology, four blood coagulation indexes, animal behavior, weight, ingestion, heart rate, syndrome rating, and red, green and blue percentage composition in tongue and paw pictures, whereas the group given Shaofu Zhuyu Tang showed no remarkable improvement. The evaluation system for the animal model with gynecological disease characterized by Qi stagnation and blood stasis syndrome is established to provide reference for studies on the evaluation system for qi stagnation and blood stasis syndrome models.

Physical Exercise Prevents Stress-Induced Activation of Granule Neurons and Enhances Local Inhibitory Mechanisms in the Dentate Gyrus

Physical exercise is known to reduce anxiety. The ventral hippocampus has been linked to anxiety regulation but the effects of running on this subregion of the hippocampus have been incompletely explored. Here, we investigated the effects of cold water stress on the hippocampus of sedentary and runner mice and found that while stress increases expression of the protein products of the immediate early genes c-fos and arc in new and mature granule neurons in sedentary mice, it has no such effect in runners. We further showed that running enhances local inhibitory mechanisms in the hippocampus, including increases in stress-induced activation of hippocampal interneurons, expression of vesicular GABA transporter (vGAT), and extracellular GABA release during cold water swim stress. Finally, blocking GABAA receptors in the ventral hippocampus, but not the dorsal hippocampus, with the antagonist bicuculline, reverses the anxiolytic effect of running. Together, these results suggest that running improves anxiety regulation by engaging local inhibitory mechanisms in the ventral hippocampus.

The longitudinal study of rat hippocampus influenced by stress: Early adverse experience enhances hippocampal vulnerability and working memory deficit in adult rats

Epidemiologic studies indicate that early adverse experience is related to learning disabilities in adults, but the neurobiological mechanisms have not yet been identified. We used longitudinal animal experiments to test the hypothesis that early life stress enhances hippocampal vulnerability and working memory deficit in adult rats. The expression of Synaptophysin (SYN) and apoptosis (Apo) in hippocampal CA3 and dentate gyrus (DG) regions were examined to evaluate the effects of environmental factors on the hippocampus. The working memory errors via radial 8-arm maze were studied to evaluate the long-term effect of early stress on rats’ spatial learning ability. Our results indicated that chronic restraint stress in early life and forced cold water swimming stress in adulthood reduced SYN expression and increased Apo levels in rat hippocampus, but the hippocampal damage tended to recover when rats returned to a non-stress environment. In addition, when the rats were exposed to forced cold water swimming stress during adulthood, SYN expression (CA3 and DG regions) and Apo levels (CA3 region) in rat hippocampus showed statistical difference between early restraint stress group and non-early restraint stress group (rats exposed to stress in adulthood only). One month after the two groups of rats returned to non-stress environment, this difference of SYN expression (CA3 and DG regions) and working memory deficit between the two groups was still statistically significant. Our study findings suggested that early adverse experience enhances hippocampal vulnerability and working memory deficit in adult rats, and reduces structural plasticity of hippocampus.