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Abstract: Free and Easy Wanderer Plus (FEWP) is a well-known traditional Chinese medicine that has been shown to be effective in treating various mood disorders. The purpose of the present study was to determine whether FEWP could ameliorate stress-associated behavior in rats. Following the exposure to enhanced single prolonged stress (ESPS) paradigm, consisting of 2-hr constraint, 20-min forced swimming, ether-induced loss of consciousness, and an electric foot shock, animals were administered orally with FEWP (2.5, 5, or 10mg/kg daily) or vehicle for 2weeks. Animals were then tested in the open field, elevated plus-maze, and Morris water maze. ESPS exposure resulted in pronounced anxiety-like behavior, without impairing locomotor activity, as indicated by significant decreases of time spent and number of entries into open arms in the elevated plus-maze test, and unaltered distance traveled in the open field test compared to unexposed animals. ESPS-exposed animals also displayed marked cognitive impairments, with significant increases of distance traveled and the escape latency to the underwater platform, and a striking decrease of time spent in the target quadrant with and without the removal of the platform in the water maze test. However, repeated treatment with FEWP, particularly at higher doses, reversed the aforementioned behavioral values in the elevated plus-maze and water maze tests to the levels similar to unexposed animals. These results indicate that FEWP possesses anxiolytic and cognition-improving effects and may be an effective herbal preparation for the treatment of stress-associated conditions, such as posttraumatic stress disorder (PTSD). [Copyright &y& Elsevier]

Electroacupuncture (EA) is a clinically useful physiological therapy that has been recently adopted to treat several brain disorders. However, the potential role of early EA intervention in the prevention of posttraumatic stress disorder (PTSD) as well as its potential cellular and molecular mechanism has never been investigated previously. In the present study, we used an enhanced single prolonged stress (ESPS) model to access the effects of early EA intervention on the prevention of anxiety-like and fear learning behaviors, as well as the influence of the expression of post-synaptic density protein 95 (PSD95), synaptophysin (Syn), brain derived neurotrophic factor (BDNF), diacylglycerol lipase alpha (DAGLα) and cannabinoid type 1 receptor (CB1R) in the hippocampus with or without DAGLα or CB1R knockdown by a short hairpin RNA (shRNA) in the hippocampus. Moreover, the effects of electrical stimulation with different parameters on the expression of DAGLα and CB1R in the hippocampal astrocytes were also observed. The results showed that Early EA intervention improved hippocampal synaptic plasticity and ameliorated PTSD-like behaviors and also increased expression of BDNF, DAGLα and CB1R. However, either DAGLα or CB1R knockdown by a short hairpin RNA (shRNA) eliminated the neuroprotective effects of early EA intervention. Furthermore, electrical stimulation with 2/15 Hz 1 mA elevated the expression of DAGLα and CB1R. Altogether, our findings provide new insights regarding the possibility of using early EA intervention in the prevention of PTSD, and the protective effects of EA is involving the activation of DAGLα and CB1R. • Early EA intervention protects against PTSD-like behaviors. • Early EA intervention prevents hippocampal synaptic plasticity damage. • EA preventive effects in PTSD may involve the activation of DAGLα and CB1R. [ABSTRACT FROM AUTHOR]

Abstract: The present study examined the protective effect of hyperbaric oxygen preconditioning (HBO-PC) and the role of thioredoxin reductase (TrxR) in a post-traumatic stress disorder (PTSD)-induced rat model by using single prolonged stress (SPS). Rats were randomly divided into Sham, HBO, SPS and HBO+SPS groups. HBO-PC was conducted by exposing rats to 100% oxygen at 2.5atm absolute for 1h each day for 5 consecutive days. SPS was performed 24h after the last HBO-PC conditioning event. At 1h, 6h, 12h, 24h and 72h after SPS, TrxR mRNA expression was analyzed in the hippocampus; Nissl and TUNEL staining were performed at 72h after SPS. The results indicated that HBO-PC was able to significantly preserve viable neurons in the CA1 subfield of hippocampus following SPS exposure, as evidenced by reduced amounts of CA1 neuronal apoptosis. Furthermore, HBO-PC upregulate the expression of TrxR-1 and TrxR-2 mRNA in the hippocampus at 6h and 12h after SPS exposure and ameliorated anxiety-like behavior and cognitive impairments normally induced by SPS. Taken together, these findings suggest that HBO-PC is beneficial for the improvement of anxiety-like behavior and cognitive impairments induced by SPS exposure, and this effect might be associated with inhibition of neuronal apoptosis via upregulation of TrxR in stressed rats. [Copyright &y& Elsevier]

Abstract: On July 29, 2007, a severe coalmine-flooded disaster occurred in central China and 69 miners were trapped in an about 1400m underground coal pit. Fortunately, all of them were rescued after 75h of the ordeal. At 3 and 6months after the disaster, psychopathological profiles, plasma levels of cortisol and adrenocorticotropic hormone (ACTH) were evaluated in 48 survivors for posttraumatic stress disorder (PTSD) and comorbid symptoms. Magnetic resonance imaging (MRI) study was performed at 6months. The prevalence of PTSD was 35.4% (17/48) at 3months and 31.3% (15/48) at 6months post-disaster, with high rates of comorbid symptoms. Risk factors for PTSD included previous traumatic experience, less than 5years of being a miner, in an extremely exhausted or sick during the disaster, poor interpersonal relationship and poor sleep quality experienced before the disaster. Mean plasma cortisol levels at 6months, but not at 3months, were significantly higher in PTSD-positive subjects than the negative, and positively correlated with the severity of several comorbid symptoms. Either whole or regional brain volumes of PTSD-positive subjects were not significantly different from PTSD-negative subjects, but PTSD subjects had significantly reduced fractional anisotropy values in the right posterior cingulum and bilateral hippocampal body compared to subjects without PTSD. These results suggest that traumatic exposure in severe coalmining disasters results in considerable psychological consequences, with highly prevalent PTSD and comorbid symptoms, which are associated with previous traumatic experience, shorter-length underground services, and poor interpersonal relationships and sleep quality experienced before the disaster. Baseline cortisol level may be a useful biological predictor for different phases of the development of PTSD. The aberrant connectivity of the hippocampus and the cingulum may represent an early pathological response to trauma exposure. [Copyright &y& Elsevier]

Abstract: In the rat, single-prolonged stress (SPS) model produces a core symptom of post-traumatic stress disorder (PTSD), the enhanced fear response to the traumatic cue (conditioned fear response). This investigative tool is typically used for PTSD studies. However, whether SPS can produce another core symptom of PTSD, hyperarousal (the sensitized fear response in animal models), has not been evaluated. It is also not clear whether SPS can enhance both conditioned and sensitized fear responses after different incubation times. In this study, a single inescapable electric foot shock was given to rats immediately after SPS procedures (SPS&S). After different incubation times (1, 7 or 14 days), the conditioned or sensitized fear response was measured by re-exposing the stressed rats to the shock context or a neutral tone in a novel environment. Additionally, paroxetine, a selective serotonin reuptake inhibitor (SSRI) was administered after SPS&S for 14 days to test its potential preventive effect on PTSD-like symptoms. We observed that conditioned fear persisted and sensitized fear increased with ongoing incubation times after SPS&S. Early rapid intervention with paroxetine after SPS&S ameliorated PTSD-like symptoms in both fear responses and anxiety behaviors. Our data suggests that this modified SPS&S model may be both novel and predictably mimic the clinical characteristics of PTSD better than other investigative paradigms. [Copyright &y& Elsevier]