Effect of single prolonged stress in different pregnant time on the emotion and cognitive function of adult offspring rats / 中华行为医学与脑科学杂志

Objective To investigate the effect of prenatal stress (PS) at different pregnant time on emotion and cognition of adult offspring rats.Methods Twelve healthy female Sprague Dawley (SD) rats were randomly divided into control group(CON,n=4),the early pregnancy group(PS1,the 1～ 7 days of pregnancy,n=4) and the late pregnancy group(PS3,the 15 ～ 21 days of pregnancy,n=4).The pregnant rats were exposed to single-prolonged stress(SPS) on gestational day 7 or 15 respectively,except control group.The offspring were measured every weekend from 1-7 week after birth.At the eighth weekend,the sucrose intake (anhedonia) and Morris water maze (MWM) were performed to assess depression-like behavior and spatial learning and memory.Results The body weight of the first to seventh weeks after birth showed that there was a statistically significant difference among the three groups (F=28.207,P＜0.01),and there was a significant difference in time effect (F=1 041.546,P＜0.01).The body weight of two PS groups was significantly lower than those of control group(P＜0.05).The body weight of PS3 was lower than that of PS1 significantly(P＜0.05).Sucrose preference:PS3((27.70± 19.31) ％) were reductive on sucrose consumption than CON significantly((66.93±19.67) ％)(P＜0.05)while PS1 ((89.80±6.79) ％) increased in sucrose consumption compared with the CON significantly(P＜0.05).MWM:in training stage the difference of average avoid latency was existed in the three groups of the first 5 days(F=11.121,P＜0.01).Similarly,there was a significant difference in measure time(F=91.327,P＜0.01),the escape latency of the PS3 was decreased,while PS1 was significantly increased compared with CON;in testing stage,PS3 ((54.50±4.64) s,(53.21±4.45)) showed a significant increase in the duration in target site and numbers of times across the target site compared with CON((32.24±.4.17) s,(31.68±4.00)) (P＜0.05).Conclusion The acceptance of stress in the late pregnancy may lead to depression like behavior in the adult offspring and also enhance the learning and memory ability.And acceptance of stress in early pregnancy can cause impairment of learning and memory ability in adult offspring rats.

Effect of social isolation on the behavior of rat models of post-traumatic stress disorder established by single-prolonged stress / 中国比较医学杂志

Objective To establish a rat model of post-traumatic stress disorder(PTSD)through single-prolonged stress(SPS)and to observe the effect of social isolation on the behavior of the SPS model rats. Methods A total of 36 rats were randomly divided into the normal group, SPS model group and SPS combined with social isolation group. The rats in both SPS model group and SPS combined with social isolation group were modeled by single-prolonged stress,and the rats in the SPS combined with social isolation group were raised separately after modelling. The weight gaining,the total movement distance in open field test,the frequency of grid crossing,the single maximum movement distance,and the freezing frequency and time durations in the freezing behavior test were measured after 7 days of modeling. Results Compared with the normal group,the weight gaining and the single maximum movement distance of the rats in the SPS model group were significantly decreased(P < 0.01),as well as the total movement distance and the frequency of grid crossing(P < 0.05),while the freezing frequency and time in the freezing behavior test were significantly increased(P < 0.01). Compared with the normal group,the weight gaining and crossing times of the rats in the SPS combined with social isolation group was decreased(P <0.05),and the freezing frequency and time durations in the freezing behavior test were increased(P < 0.05). In addition, compared with the SPS model group,the total movement distance in the open field test,the frequency of grid crossing and the single maximum movement distance of the rats in the SPS combined with social isolation group were increased(P < 0.05). Conclusions The rat model of post-traumatic stress disorder is successfully established by single-prolonged stress, and 7 days of social isolation may alleviate the anxiety state of SPS model rats.

Berberine alleviates symptoms of anxiety by enhancing dopamine expression in rats with post-traumatic stress disorder

Post-traumatic stress disorder (PTSD) is a trauma-induced psychiatric disorder characterized by impaired fear extermination, hyperarousal, anxiety, depression, and amnesic symptoms that may involve the release of monoamines in the fear circuit. The present study measured several anxiety-related behavioral responses to examine the effects of berberine (BER) on symptoms of anxiety in rats after single prolonged stress (SPS) exposure, and to determine if BER reversed the dopamine (DA) dysfunction. Rats received BER (10, 20, or 30 mg/kg, intraperitoneally, once daily) for 14 days after SPS exposure. BER administration significantly increased the time spent in the open arms and reduced grooming behavior during the elevated plus maze test, and increased the time spent in the central zone and the number of central zone crossings in the open field test. BER restored neurochemical abnormalities and the SPS-induced decrease in DA tissue levels in the hippocampus and striatum. The increased DA concentration during BER treatment may partly be attributed to mRNA expression of tyrosine hydroxylase and the DA transporter in the hippocampus, while BER exerted no significant effects on vesicular monoamine transporter mRNA expression in the hippocampus of rats with PTSD. These results suggest that BER had anxiolytic-like effects on behavioral and biochemical measures associated with anxiety. These findings support a role for reduced anxiety altered DAergic transmission and reduced anxiety in rats with PTSD. Thus, BER may be a useful agent to treat or alleviate psychiatric disorders like those observed in patients with PTSD.

Tetramethylpyrazine reverses anxiety-like behaviors in a rat model of post-traumatic stress disorder

Post-traumatic stress disorder (PTSD) is a trauma-induced psychiatric disorder characterized by impaired fear extermination, hyperarousal, and anxiety that may involve the release of monoamines in the fear circuit. The reported pharmacological properties of tetramethylpyrazine (TMP) include anti-cancer, anti-diabetic, anti-atherosclerotic, and neuropsychiatric activities. However, the anxiolytic-like effects of TMP and its mechanism of action in PTSD are unclear. This study measured several anxiety-related behavioral responses to examine the effects of TMP on symptoms of anxiety in rats after single prolonged stress (SPS) exposure by reversing the serotonin (5-HT) and hypothalamic-pituitary-adrenal (HPA) axis dysfunction. Rats were given TMP (10, 20, or 40 mg/kg, i.p.) for 14 days after SPS exposure. Administration of TMP significantly reduced grooming behavior, increased the time spent and number of visits to the open arm in the elevated plus maze test, and significantly increased the number of central zone crossings in the open field test. TMP administration significantly reduced the freezing response to contextual fear conditioning and significantly restored the neurochemical abnormalities and the SPS-induced decrease in 5-HT tissue levels in the prefrontal cortex and hippocampus. The increased 5-HT concentration during TMP treatment might be partially attribute to the tryptophan and 5-hydroxyindoleacetic acid mRNA level expression in the hippocampus of rats with PTSD. These findings support a role for reducing the altered serotonergic transmission in rats with PTSD. TMP simultaneously attenuated the HPA axis dysfunction. Therefore, TMP may be useful for developing an agent for treating psychiatric disorders, such those observed in patients with PTSD.

Effects of systemic administration of ibuprofen on stress response in a rat model of post-traumatic stress disorder

Pro-inflammatory cytokine and brain-derived neurotrophic factor (BDNF) are modulated in post-traumatic stress disorder (PTSD). This study investigated the effects of ibuprofen (IBU) on enhanced anxiety in a rat model of PTSD induced by a single prolonged stress (SPS) procedure. The effects of IBU on inflammation and BDNF modulation in the hippocampus and the mechanisms underlying for anxiolytic action of IBU were also investigated. Male Sprague-Dawley rats were given IBU (20 or 40 mg/kg, i.p., once daily) for 14 days. Daily IBU (40 mg/kg) administration signifi cantly increased the number and duration of open arm visits in the elevated plus maze (EPM) test, reduced the anxiety index in the EPM test, and increased the time spent in the center of an open fi eld after SPS. IBU administration signifi cantly decreased the expression of pro-inflammatory mediators, such as tumor necrosis factor-α, interleukin-1β, and BDNF, in the hippocampus, as assessed by reverse transcription-polymerase chain reaction analysis and immunohistochemistry. These fi ndings suggest that IBU exerts a therapeutic effect on PTSD that might be at least partially mediated by alleviation of anxiety symptoms due to its anti-inflammatory activity and BDNF expression in the rat brain.

The effect of environmental on spontaneous activities and expression of c-Fos, 5-HT in the hippocampal neurons of rats with posttraumatic stress disorder / 中华行为医学与脑科学杂志

Objective To investigate the expressions of c-Fos,5-HT and spontaneous activities in single prolonged stress (SPS) stress rats,and to study the possible mechanism of posttraumatic stress disorder(PTSD).Methods forty-eight male SD rats were randomly divided into 6 groups:Individual living + SPS group (IS group),Individual living+control group (IC group),Enriched environment+SPS group (ES group),Enriched environment+control group (EC group),control+SPS group(CS group),control group(C group),8 rats in each group,spontaneous activities were measured before the experiment and post experiment at week 1,2.And the expressions of c-Fos,5-HT in the hippocampus were examined by immunohistochemical staining.Results (1) Spontaneous activity:there were no differences of crossing number and distance among 6 groups before experiment (P＞0.05).On SPS 14 days the crossing number and distance of IS group (12.12±9.64,(2.71 ± 1.99)m) decreased compared with the CS group(45.25±8.37,(6.37± 1.18) m,P＜0.05),and ES group (69.75± 10.05,(10.69± 1.50) m)showed significant increase compared with CS group (P＜0.05).(2)5-HT:the expression of 5-HT in the hippocampus of IS group(0.1125±0.0095) was significantly higher than that in CS group(0.6138±0.0059,P＜0.05),menwhile lower in ES group(0.0495±0.0074,P＜0.05).(3)c-Fos:compared with CS group(0.3108±0.0074),the expression of c-Fos in the hippocampus of IS group(0.3585±0.0150,P＜0.05) significantly increased,but decreased in ES group (0.2613±0.0063,P＜ 0.05).Conclusion Enriched environmental can improve the level of activities in PTSD rats,and to reduce the the expression of c-Fos and 5-HT in the hippocampal neurons.

L-Tetrahydropalmatine Ameliorates Development of Anxiety and Depression-Related Symptoms Induced by Single Prolonged Stress in Rats

Abnormal adaptation of the stress-response system following traumatic stress can lead to alterations in the hypothalamic-pituitary-adrenal (HPA) axis that may contribute to the development of post-traumatic stress disorder (PTSD). The present study used several behavioral tests to investigate the anxiolytic-like and antidepressant activity of L-tetrahydropalmatine (L-THP) in an experimental rat model of anxiety and depression induced by single prolonged stress (SPS), an animal model of PTSD. Male rats were treated intraperitoneally (i.p.) with vehicle or varied doses of THP 30 min prior to SPS for 8 consecutive days. Daily THP (50 mg/kg) administration significantly increased the number and duration of open arm visits in the elevated plus maze (EPM) test, reduced the anxiety index, increased the risk assessment, and increased the number of head dips over the borders of the open arms after SPS. THP was also associated with increased time spent at the center of the open field, reduced grooming behaviors in the EPM test, and reduced time spent immobile in the forced swimming test (FST). It also blocked the decrease in neuropeptide Y (NPY) and the increase in corticotrophin-releasing factor (CRF) expression in the hypothalamus. This is the first study to determine that THP exerts pronounced anxiolytic-like and antidepressant effects on the development of the behavioral and biochemical symptoms associated with PTSD, indicating its prophylactic potential. Thus, THP reversed several behavioral impairments triggered by the traumatic stress of SPS and is a potential non-invasive therapeutic intervention for PTSD.

A preliminary study of single prolonged stress influence acoustic startle reflex and prepulse inhibition in rats / 中华行为医学与脑科学杂志

ObjectiveTo explore the deficits of acoustic startle reflex (ASR) and prepulse inhibition (PPI) of acoustic startle reflex in single prolonged stress rats.MethodsSixty Sprague Dawley rats were randomly divided into control 1,7,14 d groups and stress 1,7,14 d groups.All stressed rats received single prolonged stress while all control rats were left in their home cage.Behavioral changes in these rats were analyzed in ASR and PPI paradigm.ASR and PPI were carried out on day 2,8,15,respectively.ResultsThere were no differences of ASR and PPI among control 1,7,14 d groups (P ＞ 0.05).ASR of stress 1 d group ( (92.49 ± 31.54) g) was higher than that of control 1 d group((64.48 ± 17.95)g,P＜0.05) while PPI of stress 1 d group((28.60 ±29.02)％) was lower than that of control 1 d group( (41.60 ± 15.10)％,P ＜ 0.05 ).There were no differences of ASR between control 7 d group and stress 7 d group,control 14 d group and stress 14 d group (P＞ 0.05 ).Compared with control 7 d group ( (41.30 ± 12.79) ％ ),PPI in stress 7 d group ( ( 17.95 ± 31.79) ％ ) was reduced (P ＜ 0.05 ).Compared with control 14 d group ( (41.16 ± 12.25 ) ％ ),PPI in stress 14 d group( ( 13.71 ± 32.48) ％ ) was reduced (P ＜ 0.05).ConclusionEffects of stress on ASR in rats increased in early period,while the impaired PPI may last for a long time.