Neurofeedback Improves Memory and Peak Alpha Frequency in Individuals with Mild Cognitive Impairment.

Mild cognitive impairment (MCI) is a syndrome characterized by a decrease in cognitive abilities, while daily function is maintained. This condition, which is associated with an increased risk for the development of Alzheimer's disease, has no known definitive treatment at present. In this open-label pilot study we explored the possible benefits of neurofeedback for subjects with MCI. Eleven participants diagnosed with MCI were trained to increase the power of their individual upper alpha band of the electroencephalogram (EEG) signal over the central parietal region. This was achieved using an EEG-based neurofeedback training protocol. Training comprised ten 30-min sessions delivered over 5 weeks. Cognitive and electroencephalographic assessments were conducted before and after training and at 30 days following the last training session. A dose-dependent increase in peak alpha frequency was observed throughout the period of training. Memory performance also improved significantly following training, and this improvement was maintained at 30-day follow-up, while peak alpha frequency returned to baseline at this evaluation. Our findings suggest that neurofeedback may improve memory performance in subjects with mild cognitive impairment, and this benefit may be maintained beyond the training period.

Adjunctive treatment with brexpiprazole and escitalopram reduces behavioral stress responses and increase hypothalamic NPY immunoreactivity in a rat model of PTSD-like symptoms.

The study explored effects of brexpiprazole (partial D2/5-HT1A agonist, 5-HT2A and α1B/2C-adrenoceptor antagonist) in rats exposed to predator scent stress (PSS), a proposed model of PTSD-like phenotype. Brexpiprazole (3.0mg/kg, PO), escitalopram (5.0mg/kg, IP) and their combination were administered twice daily for 14 days, starting 14 days after exposure to PSS or sham-PSS, shortly after a situational stress reminder. One day after last treatment behavioral responsivity was assessed. Brexpiprazole+escitalopram-treated rats spent more time in open arms, entered open arms more often and exhibited a lower anxiety index in the elevated plus maze than vehicle-treated, PSS-exposed rats. Adjunct brexpiprazole+escitalopram treatment reduced startle amplitude, compared with vehicle-treated, PSS-exposed rats. Treatment with either drug alone did not attenuate anxiety-like behaviors following PSS exposure. Use of cut-off behavioral criteria confirmed that adjunct treatment shifted prevalence of PSS-exposed rats from extreme towards minimal behavioral responders. One day following behavioral tests, brains were prepared for immunohistochemical analysis of number of BDNF-positive cells and of NPY-positive cells/fibers. PSS exposure decreased BDNF levels in hippocampus, but this was not affected by drug treatments. PSS exposure decreased number of NPY positive cells/fibers in paraventricular and arcuate nuclei of hypothalamus. Adjunct treatment with brexpiprazole+escitalopram increased NPY in PSS- and sham-exposed rats. Treatment with brexpiprazole alone had no effects, while treatment with escitalopram alone increased NPY in the arcuate nucleus of PSS-exposed rats. In conclusion, treatment with brexpiprazole+escitalopram may be an effective intervention for the attenuation of PTSD-like stress responses, which in part may be mediated by activating NPY function.

Blunted basal corticosterone pulsatility predicts post-exposure susceptibility to PTSD phenotype in rats.

The basal activity of the hypothalamic-pituitary-adrenal axis is highly dynamic and is characterized by both circadian and ultradian (pulsatile) patterns of hormone secretion. Pulsatility of glucocorticoids has been determined to be critical for optimal transcriptional, neuroendocrine, and behavioral responses. We used an animal model of post-traumatic stress disorder (PTSD) to assess whether stress-induced impairment of behavioral responses is correlated with aberrant secretion of corticosterone. Serial blood samples were collected manually via the jugular vein cannula during the light-(inactive)-phase in conscious male rats at 20-min intervals for a period of 5h before and 6.5h after exposure to predator scent stress. The outcome measures included behavior in an elevated plus-maze and acoustic startle response 7days after exposure. Individual animals were retrospectively classified as having "extreme", "partial", or "minimal" behavioral responses according to pre-set cut-off criteria for behavioral response patterns. Corticosterone secretion patterns were analyzed retrospectively. Under basal conditions, the amplitude of ultradian oscillations of corticosterone levels, rather than the mean corticosterone level or the frequency of corticosterone pulsatility, was significantly reduced in individuals who displayed PTSD-phenotype 8days later. In addition, extreme disruption of behavior on day 8 post-exposure was also characterized by a blunting of corticosterone response to the stressor. Animals with behavior that was only partially affected or unaffected displayed none of the above changes. Blunted basal corticosterone pulse amplitude is a pre-existing susceptibility or risk factor for PTSD, which originates from prior (life) experiences and may therefore predict post-exposure PTSD-phenotype in rats.

Controlled Low-Pressure Blast-Wave Exposure Causes Distinct Behavioral and Morphological Responses Modelling Mild Traumatic Brain Injury, Post-Traumatic Stress Disorder, and Comorbid Mild Traumatic Brain Injury-Post-Traumatic Stress Disorder.

The intense focus in the clinical literature on the mental and neurocognitive sequelae of explosive blast-wave exposure, especially when comorbid with post-traumatic stress-related disorders (PTSD) is justified, and warrants the design of translationally valid animal studies to provide valid complementary basic data. We employed a controlled experimental blast-wave paradigm in which unanesthetized animals were exposed to visual, auditory, olfactory, and tactile effects of an explosive blast-wave produced by exploding a thin copper wire. By combining cognitive-behavioral paradigms and ex vivo brain MRI to assess mild traumatic brain injury (mTBI) phenotype with a validated behavioral model for PTSD, complemented by morphological assessments, this study sought to examine our ability to evaluate the biobehavioral effects of low-intensity blast overpressure on rats, in a translationally valid manner. There were no significant differences between blast- and sham-exposed rats on motor coordination and strength, or sensory function. Whereas most male rats exposed to the blast-wave displayed normal behavioral and cognitive responses, 23.6% of the rats displayed a significant retardation of spatial learning acquisition, fulfilling criteria for mTBI-like responses. In addition, 5.4% of the blast-exposed animals displayed an extreme response in the behavioral tasks used to define PTSD-like criteria, whereas 10.9% of the rats developed both long-lasting and progressively worsening behavioral and cognitive "symptoms," suggesting comorbid PTSD-mTBI-like behavioral and cognitive response patterns. Neither group displayed changes on MRI. Exposure to experimental blast-wave elicited distinct behavioral and morphological responses modelling mTBI-like, PTSD-like, and comorbid mTBI-PTSD-like responses. This experimental animal model can be a useful tool for elucidating neurobiological mechanisms underlying the effects of blast-wave-induced mTBI and PTSD and comorbid mTBI-PTSD.

Distinctive cardiac autonomic dysfunction following stress exposure in both sexes in an animal model of PTSD.

It is unclear whether the poor autonomic flexibility or dysregulation observed in patients with posttraumatic stress disorder (PTSD) represents a pre-trauma vulnerability factor or results from exposure to trauma. We used an animal model of PTSD to assess the association between the behavioral response to predator scent stress (PSS) and the cardiac autonomic modulation in male and female rats. The rats were surgically implanted with radiotelemetry devices to measure their electrocardiograms and locomotor activity (LMA). Following baseline telemetric monitoring, the animals were exposed to PSS or sham-PSS. Continuous telemetric monitoring (24h/day sampling) was performed over the course of 7days. The electrocardiographic recordings were analyzed using the time- and frequency-domain indexes of heart rate variability (HRV). The behavioral response patterns were assessed using the elevated plus maze and acoustic startle response paradigms for the retrospective classification of individuals according to the PTSD-related cut-off behavioral criteria. During resting conditions, the male rats had significantly higher heart rates (HR) and lower HRV parameters than the female rats during both the active and inactive phases of the daily cycle. Immediately after PSS exposure, both the female and male rats demonstrated a robust increase in HR and a marked drop in HRV parameters, with a shift of sympathovagal balance towards sympathetic predominance. In both sexes, autonomic system habituation and recovery were selectively inhibited in the rats whose behavior was extremely disrupted after exposure to PSS. However, in the female rats, exposure to the PSS produced fewer EBR rats, with a more rapid recovery curve than that of the male rats. PSS did not induce changes to the circadian rhythm of the LMA. According to our results, PTSD can be conceptualized as a disorder that is related to failure-of-recovery mechanisms that impede the restitution of physiological homeostasis.

[NONINVASIVE BRAIN STIMULATION IN NEUROPSYCHIATRIC DISORDERS].

INTRODUCTION: Noninvasive brain stimulation is a growing field of treatment for many neuropsychiatric problems. In this review, several of the more common brain stimulation devices are presented. Specifically, we will review Transcranial Magnetic Stimulation (TMS), Transcranial Direct Current Stimulation (tDCS), Alternating Current Stimulation (ACS), Infrared Stimulation, Electroencephalography Neurofeedback (EEG-NF) and functional Magnetic Resonance Imagining Neurofeedback (fMRI-NF). We will outline some of the properties of these devices including the mechanism, side effect profile, using sham for research and major future developments.

Evaluating low-resolution tomography neurofeedback by single dissociation of mental grotation task from stop signal task performance.

Electroencephalography source localization neurofeedback, i.e Standardized low-resolution tomography (sLORETA) neurofeedback are non-invasive method for altering region specific brain activity. This is an improvement over traditional neurofeedback which were based on recordings from a single scalp-electrode. We proposed three criteria clusters as a methodological framework to evaluate electroencephalography source localization neurofeedback and present relevant data. Our objective was to evaluate standardized low resolution EEG tomography neurofeedback by examining how training one neuroanatomical area effects the mental rotation task (which is related to the activity of bilateral Parietal regions) and the stop-signal test (which is related to frontal structures). Twelve healthy participants were enrolled in a single session sLORETA neurofeedback protocol. The participants completed both the mental rotation task and the stop-signal test before and after one sLORETA neurofeedback session. During sLORETA neurofeedback sessions participants watched one sitcom episode while the picture quality co-varied with activity in the superior parietal lobule. Participants were rewarded for increasing activity in this region only. Results showed a significant reaction time decrease and an increase in accuracy after sLORETA neurofeedback on the mental rotation task but not after stop signal task. Together with behavioral changes a significant activity increase was found at the left parietal brain after sLORETA neurofeedback compared with baseline. We concluded that activity increase in the parietal region had a specific effect on the mental rotation task. Tasks unrelated to parietal brain activity were unaffected. Therefore, sLORETA neurofeedback could be used as a research, or clinical tool for cognitive disorders.

ß-Alanine supplemented diets enhance behavioral resilience to stress exposure in an animal model of PTSD.

This study investigated the effects of ß-alanine (BA) ingestion on the behavioral and neuroendocrine response of post-traumatic stress disorder (PTSD) in a murine model. Animals were fed a normal diet with or without (PL) BA supplementation (100 mg kg(-1)) for 30 days. Animals were then exposed to a predator-scent stress (PSS) or a sham (UNEX). Behaviors were evaluated using an elevated plus maze (EPM) and acoustic startle response (ASR) 7 days following exposure to the PSS. Corticosterone concentrations (CS), expression of brain-derived neurotrophic factor (BDNF), and brain carnosine concentrations were analyzed a day later. Animals in PSS+PL spent significantly less time in the open arms and in the number of entries in the EPM than PSS+BA, UNEX+BA, or UNEX+PL. Animals in PSS+BA had comparable scores to UNEX+BA. Anxiety index was higher (p < 0.05) in PSS+PL compared to PSS+BA or animals that were unexposed. ASR and freezing were greater (p < 0.05) in animals exposed to PSS compared to animals unexposed. CS expression was higher (p < 0.05) in animals exposed to PSS compared to unexposed animals. Brain carnosine concentrations in the hippocampus and other brain sections were significantly greater in animals supplemented with BA compared to PL. BDNF expression in the CA1 and DG subregions of the hippocampus was lower (p < 0.05) in animals exposed and fed a normal diet compared to animals exposed and supplemented with BA, or animals unexposed. In conclusion, BA supplementation in rats increased brain carnosine concentrations and resulted in a reduction in PTSD-like behavior, which may be mediated in part by maintaining BDNF expression in the hippocampus.

Beyond the HPA-axis: The role of the gonadal steroid hormone receptors in modulating stress-related responses in an animal model of PTSD.

The hypothalamic-pituitary-adrenal (HPA) axis, which plays a major role in the response to stress, and the hypothalamic-pituitary-gonadal (HPG) axis are closely linked with the ability to inhibit the other. Testosterone, a product of the HPG, has many beneficial effects beyond its functions as a sex hormone including anti-anxiety properties. In this study we examined the effect of stress exposure on gonadal hormones, and their efficacy in modulating anxiety-like response in an animal model of PTSD. Male rats were exposed to predator scent stress, followed by analysis of brain expression of androgen receptor (AR) receptor and estrogen receptor α (ERα). The behavioral effects of immediate treatment with testosterone, testosterone receptor antagonist (flutamide) or vehicle were evaluated using the elevated plus-maze, acoustic startle response and trauma-cue response. Levels of circulating corticosterone and testosterone were also measured after treatment. The behavioral effects of delayed testosterone treatment were explored in the same manner. We report that animals whose behavior was extremely disrupted (EBR) selectively displayed significant down-regulation of AR and ERα in the hippocampus. Immediate treatment with flutamide or delayed treatment with testosterone significantly increased prevalence rates of minimal behavioral response (MBR) and decreased prevalence of EBR with favorable behavioral results. Testosterone levels were higher in control un-exposed animals, while corticosterone was higher in control exposed animals. This study suggests that gonadal steroid hormones are involved in the neurobiological response to predator scent stress and thus warrant further study as a potential therapeutic avenue for the treatment of anxiety-related disorders.

Early post-stressor intervention with minocycline, a second-generation tetracycline, attenuates post-traumatic stress response in an animal model of PTSD.

We assessed the effects of minocycline, a tetracycline with anti-inflammatory, anti-apoptotic and neuroprotective capacities, in an animal model of post-traumatic stress disorder (PTSD). Rats were exposed to psychogenic stress and treated 1h later with minocycline or saline. Behavioral measures included the elevated plus-maze (EPM) and acoustic startle response (ASR) 7 days post stress-exposure. One day after behavioral testing, animals were exposed to a trauma cue and freezing response was assessed. Local levels of cytokines interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the hippocampus, frontal cortex (FC) and hypothalamus were then examined. Minocycline attenuated anxious-like behaviors in stress-exposed rats. In addition, decreased levels of cytokines were measured in exposed rats treated with minocycline compared to their counterparts treated with saline. This study suggests a potential use of minocycline in preventing physiological and behavioral alternations resulting from acute exposure to psychological stress. As this is the first study to report beneficial outcomes for minocycline treatment in an animal model of PTSD, further investigations of the use of minocycline in stress-related conditions with emphasis on PTSD is needed.

Immediate ketamine treatment does not prevent posttraumatic stress responses in an animal model for PTSD.

Clinical studies suggest that administration of ketamine hydrochloride-an antagonist at the N-methyl-d-aspartate ionophore-provides short-term amelioration for depressive symptoms. The effects of a brief course of ketamine given immediately following exposure to psychogenic stress on the behavioral stress responses were assessed in an animal model of posttraumatic stress disorder. Animals exposed to stress were treated 1h later with ketamine (0.5, 5, and 15 mg/kg) or vehicle for three days (N = 107). Outcome measures included behavior in the elevated plus maze (EPM) and acoustic startle response (ASR) tests 30 days after initial exposure and freezing behavior upon exposure to a trauma-cue on day 31. Pre-set cut-off behavioral criteria classified exposed animals according to their EPM and ASR response-patterns into "extreme," "minimal," or "partial" behavioral response for analysis of prevalence rates of "PTSD-like behavior." Circulating corticosterone levels were assessed 20 min after injection of ketamine in exposed and unexposed animals (N = 62). The dexamethasone suppression test was used to assess negative feedback inhibition of the HPA axis. Prevalence rates of extremely-, partially-, or minimally-disrupted behavior demonstrated that ketamine administered immediately following stress exposure was ineffective in alleviating "PTSD-like behavior" at day 30 after exposure. Administration of ketamine was associated with increase in freezing behavior after exposure to a trauma-cue on day 31. Corticosterone levels were significantly suppressed by ketamine only in the exposed animals. Administration of ketamine immediately following trauma-exposure may not only be ineffective but actually detrimental in the long term. A disruption of the post-stress HPA-response has been raised as a contributing factor.

Post-exposure sleep deprivation facilitates correctly timed interactions between glucocorticoid and adrenergic systems, which attenuate traumatic stress responses.

Reliable evidence supports the role of sleep in learning and memory processes. In rodents, sleep deprivation (SD) negatively affects consolidation of hippocampus-dependent memories. As memory is integral to post-traumatic stress symptoms, the effects of post-exposure SD on various aspect of the response to stress in a controlled, prospective animal model of post-traumatic stress disorder (PTSD) were evaluated. Rats were deprived of sleep for 6 h throughout the first resting phase after predator scent stress exposure. Behaviors in the elevated plus-maze and acoustic startle response tests were assessed 7 days later, and served for classification into behavioral response groups. Freezing response to a trauma reminder was assessed on day 8. Urine samples were collected daily for corticosterone levels, and heart rate (HR) was also measured. Finally, the impact of manipulating the hypothalamus-pituitary-adrenal axis and adrenergic activity before SD was assessed. Mifepristone (MIFE) and epinephrine (EPI) were administered systemically 10-min post-stress exposure and behavioral responses and response to trauma reminder were measured on days 7-8. Hippocampal expression of glucocorticoid receptors (GRs) and morphological assessment of arborization and dendritic spines were subsequently evaluated. Post-exposure SD effectively ameliorated long-term, stress-induced, PTSD-like behavioral disruptions, reduced trauma reminder freezing responses, and decreased hippocampal expression of GR compared with exposed-untreated controls. Although urine corticosterone levels were significantly elevated 1 h after SD and the HR was attenuated, antagonizing GRs with MIFE or stimulation of adrenergic activity with EPI effectively abolished the effect of SD. MIFE- and EPI-treated animals clearly demonstrated significantly lower total dendritic length, fewer branches and lower spine density along dentate gyrus dendrites with increased levels of GR expression 8 days after exposure, as compared with exposed-SD animals. Intentional prevention of sleep in the early aftermath of stress exposure may well be beneficial in attenuating traumatic stress-related sequelae. Post-exposure SD may disrupt the consolidation of aversive or fearful memories by facilitating correctly timed interactions between glucocorticoid and adrenergic systems.

High dose hydrocortisone immediately after trauma may alter the trajectory of PTSD: interplay between clinical and animal studies.

High-dose corticosteroids have been reported to reduce symptoms of acute stress and post-traumatic stress in polytrauma patients and in animal studies. The underlying mechanism of action remains largely unclear. These issues were addressed in parallel in the clinical and preclinical studies below. In this preliminary study, 25 patients with acute stress symptoms were administered a single intravenous bolus of high-dose hydrocortisone (100-140 mg) or placebo within 6 h of a traumatic event in a prospective, randomized, double-blind, placebo-controlled pilot study. Early single high-dose hydrocortisone intervention attenuated the core symptoms of both the acute stress and of subsequent PTSD in patients. High-dose hydrocortisone treatment given in the first few hours after a traumatic experience was associated with significant favorable changes in the trajectory of exposure to trauma, as expressed by the reduced risk of the development of PTSD post-trauma. In parallel, a comparative study of morphological arborization in dentate gyrus and its modulating molecules was performed in stress-exposed animals treated with high-dose hydrocortisone. Steroid-treated stressed animals displayed significantly increased dendritic growth and spine density, with increased levels of brain-derived neurotrophic factor (BDNF) and obtunded postsynaptic density-95 (PSD-95) levels. The animal study provided insights into the potential mechanism of this intervention, as it identified relevant morphological and biochemical associations to the clinical observations. Thus, evidence from clinical and animal studies suggests that there is a "window of opportunity" in the early aftermath of trauma to help those who are vulnerable to the development of chronic PTSD.

Alprazolam treatment immediately after stress exposure interferes with the normal HPA-stress response and increases vulnerability to subsequent stress in an animal model of PTSD.

BACKGROUND: In light of clinical reports suggesting that early benzodiazepine administration interferes with long-term recovery from traumatic stress, a prospective animal model for PTSD was employed to assess the short- and long-term effects of a brief course of alprazolam following stress exposure. METHOD: Animals exposed to stress were treated either 1 h or 7 days later with alprazolam or vehicle for 3-days. Outcome measures included behavior in the elevated plus-maze (EPM) and acoustic startle response (ASR) tests 30 days after initial exposure and freezing behavior upon exposure to a trauma-cue on day 31. One group was repeatedly exposed to the triggering trauma shortly before and after treatment and assessed as above. Circulating corticosterone levels were assessed 4 h after initiation of alprazolam and post-treatment. Pre-set cut-off behavioral criteria classified exposed animals according to their EPM and ASR response-patterns into 'extreme', 'minimal,' or 'partial' behavioral response for analysis of prevalence rates. RESULTS: Immediate alprazolam treatment was effective in alleviating anxiety at day 4. No observable anxiolytic effects remained at day 30. Immediate alprazolam also resulted in significantly greater freezing response to trauma-cue exposure and in extreme responses to double-exposure. Corticosterone levels were significantly suppressed by alprazolam during treatment and rebounded after cessation. CONCLUSION: A brief course of alprazolam in the immediate aftermath of stress-exposure is associated with less favorable responses to additional stress-exposure later on. Alprazolam was associated with a significant attenuation of the HPA-response, suggesting a possible link between initial HPA-axis response disruption and the subsequent unfavorable outcomes.

A naturalistic prospective open study of the effects of adjunctive therapy of sexual dysfunction in chronic PTSD patients.

INTRODUCTION: Post-traumatic Stress Disorder (PTSD) symptoms cause dysfunction in broad areas of patients' lives and those of their families. Sexual dysfunction (SD) is common in these patients and aggravates their distress, affecting overall sexual activity, desire, arousal, orgasm, activity and satisfaction. PTSD clinic patients are frequently referred for consultation and treatment in the SD clinic. This prospective naturalistic follow-up study of a random group of patients was intended to evaluate response to pharmacologic and psychotherapeutic interventions for SD, in terms of both sexual functioning and overall symptomatology. METHODS: Ten patients fulfilling DSM-IV diagnostic criteria for PTSD (one woman and nine men) were recruited. Treatment for the sexual symptoms was tailored individually and was administered in addition to the continuing (stable) treatment in the PTSD clinic. RESULTS: After two months of treatment for the sexual symptoms, statistically significant improvements in all domains of sexual functioning were observed. In parallel, statistically significant improvements in all domains of the Impact of Events Scale scores were observed, both on the avoidance and intrusive subscales. There were no significant differences in response to treatment in terms of time elapsed since the onset of PTSD, or the pattern or severity of sexual and PTSD symptoms. CONCLUSIONS: The results of this modest study demonstrate the importance of relating to the SD of PTSD patients irrespective of the duration or severity of their disorder. In this mixed group of PTSD patients with varied duration of symptoms, both SD and PTSD core symptoms improved significantly in response to individually tailored adjunctive treatment of the SD.

Early post-stressor intervention with high-dose corticosterone attenuates posttraumatic stress response in an animal model of posttraumatic stress disorder.

BACKGROUND: The therapeutic value of corticosteroids in the aftermath of traumatic experience has been questioned. We used an animal model of posttraumatic stress disorder (PTSD) to assess long-term behavioral effects of a single administration of various doses of corticosterone (CORT), administered immediately after exposure to psychogenic stress. METHODS: Animals were exposed to predator scent stress and treated 1 hour later with various doses of CORT or saline. The outcome measures included behavior in an elevated plus-maze (EPM) and acoustic startle response (ASR) 30 days after the initial exposure and freezing behavior upon exposure to a trauma-related cue on day 31. Pre-set cut-off behavioral criteria (CBC) classified exposed animals according to behavioral responses in EPM and ASR paradigms as those with "extreme behavioral response," "minimal behavioral response," or "intermediate response." Non-spatial memory task and 24-hour locomotor activity were assessed immediately after injection with CORT or vehicle. RESULTS: Early treatment with high-dose CORT reduced the prevalence of PTSD-like behavioral responses relative to saline-control treatment. Cue-induced freezing was significantly lower in the high-dose CORT-treated group. Lower doses of CORT significantly increased anxiety-like behavior, mean startle amplitude, and prevalence of PTSD-like behavioral disruptions, compared with saline-control treatment. The attenuated cue-responsiveness and impaired performance on a memory task imply that one key factor in this effect is the disruption of traumatic memory consolidation. CONCLUSIONS: Single treatment with high-dose CORT immediately after stressful exposure reduces the prevalence rate of extreme behavioral disruption 30 days later. Corticosterone might disrupt the consolidation of aversive or fearful memories.

Brief post-stressor treatment with pregabalin in an animal model for PTSD: short-term anxiolytic effects without long-term anxiogenic effect.

BACKGROUND: The short- and long-term behavioral effects of a brief course of pregabalin, an antiepileptic structural analogue of alpha-aminobyturic acid with analgesic and anxiolytic effects, were assessed in an animal model of post-traumatic stress disorder (PTSD). METHOD: Two-hundred thirty-three adult male Sprague-Dawley rats were employed. Behavioral responses to traumatic stress exposure (predator urine scent) were assessed immediately after (1 h) and 30 days after treatment with saline or pregabalin (at doses of 30, 100 and 300 mg/kg) in terms of behavior in the elevated plus maze (EPM) and the acoustic startle response (ASR) paradigms. At day 31 the freezing response to a trauma cue (clean cat litter) was assessed. The same treatment regimen initiated at day 7 was assessed at day 30 and in response to the trauma cue on day 31 in a separate experiment. RESULTS: In the short term, doses of 100 mg/kg and 300 mg/kg of pregabalin effectively attenuated anxiety-like behaviors. In the longer-term, pregabalin did not attenuate the onset of PTSD-like behaviors or the prevalence rates of severe cue-responses, for either the immediate or the delayed treatment regimens. CONCLUSION: Pregabalin may present an alternative compound for acute anxiolytic treatment after exposure to trauma, but has no long-term protective/preventive effects.

Post-traumatic stress behavioural responses in inbred mouse strains: can genetic predisposition explain phenotypic vulnerability?

Clinical studies of twin pairs and families of post-traumatic stress disorder (PTSD) patients raise questions as to possible genetic predisposition to PTSD. Studies using isogenic animal populations exposed to a stress paradigm could elucidate the relative contributions of genotype and environment to endophenotypic expression. The prevalence of individuals displaying severely compromised behavioural responses to predator scent stress (PSS) was assessed in six inbred strains of mice in an animal model of PTSD that classifies individuals into groups according to the degree of their behavioural response. The choice of strains was based on the frequent use of these mice in transgenic research. The prevalence of extreme behavioural response in the elevated plus maze and the acoustic startle response paradigms, performed in sequence, was assessed at baseline and 7 d after PSS exposure between and within strains, and compared to differences in circulating corticosterone levels. Narrow-sense trait heritability was determined by comparing the between-strain variance to the total variance. Although strain-specific differences in anxiety-like behaviours were demonstrated, the results revealed a significant degree of individual variability in response patterns within each of the inbred strains, yielding a baseline heritability factor for anxiety-like behaviours of 30%, but only 10% for response to stress exposure. Baseline anxiety-like behaviours were found not to be predictive of post-exposure behavioural responses. The response of the individual to stress is multifactorial and environmental factors play a predominant role in characterizing the individual response to stress exposure, although there are significant genetic underpinnings.

Rapid eye movements for acute stress disorder using video conference communication.

In order to effectively reduce the risk of developing long-lasting mental disorders in the aftermath of traumatic stress exposure, interventions must be offered early on. Therefore, access to expert assistance can have significant effects on prognosis. Rapid eye movements are part of the Eye Movement Desensitization and Reprocessing procedure that gained considerable attention in previous years. The authors present a patient suffering from an acute stress disorder, treated by rapid eye movements through telepsychiatry services.

Long-term down-regulation of BDNF mRNA in rat hippocampal CA1 subregion correlates with PTSD-like behavioural stress response.

Brain-derived neurotrophic factor (BDNF) and its intracellular kinase-activating receptor TrkB, have been implicated in the neurobiological mechanisms underlying the clinical manifestations of PTSD, especially those related to synaptic efficacy and neural plasticity. BDNF interacts with components of the stress response such as corticosterone, and plays an important role in growth, maintenance and functioning of several neuronal systems. This study employed an animal model of PTSD to investigate the relationship between prevalence rates of distinct patterns of behavioural responses to predator stress, circulating levels of corticosterone and local levels of mRNA for BDNF, TrkB and two other neurotrophic factors in selected brain areas. Animals whose behaviour was extremely disrupted by exposure selectively displayed significant down-regulation of mRNA for BDNF and up-regulation of TrkB mRNA in the CA1 subregion of the hippocampus, compared to animals whose behaviour was minimally or partially affected and to unexposed controls. The response was consistent throughout the entire study only in CA1. The consistent long-term the BDNF down-regulation and TrkB up-regulation associated with extreme behavioural compromise may be associated with chronic stress-induced psychopathological processes, especially in the hippocampus. The corresponding changes in neural plasticity and synaptic functioning may mediate clinical manifestations of PTSD.