Should Catatonia Be Conceptualized as a Pathological Response to Trauma?

ABSTRACT: Although catatonia is related to several medical conditions, catatonia as a response to trauma and posttraumatic stress disorder (PTSD) is less clear. The aim of this review is to explore the small emerging body of preliminary evidence that suggests a possible correlation between psychological trauma and catatonia. Initial data suggests a correlation between episodes of intense fear associated with trauma and PTSD and some forms of catatonic responses. Although this relationship is still speculative to be causative, it can have important implications if confirmed. This is especially salient when it is examined alongside existing studies of the response to fear in animals and the phenomenon of tonic immobility, which bears a striking resemblance to catatonia in humans. If prospective studies further support the initial findings, it could change our conceptual understanding of the etiology of a subtype of catatonia substantially while pointing to likely targets of further research to understand the biological mechanisms that underlie the illness.

Behavioral coping strategies predict tumor development and behavioral impairment after chronic social stress in mice.

The aims of this study were to identify behavioral strategies to cope with social defeat, evaluate their impact on tumor development and analyze the contributions of both to changes in physiology and behavior produced by chronic defeat stress. For this purpose, OF1 mice were inoculated with B16F10 melanoma cells and subjected to 18 days of repeated defeat stress in the presence of a resident selected for consistent levels of aggression. Combined cluster and discriminant analyses of behavior that manifested during the first social interaction identified three types of behavioral profiles: active/aggressive (AA), passive/reactive (PR) and an intermediate active/non-aggressive (ANA) profile. Animals that showed a PR coping strategy developed more pulmonary metastases at the end of the social stress period than animals in other groups. The ANA but not AA group also showed higher tumor metastases than non-stressed subjects. In addition, the ANA group differed from the other groups because it displayed the highest corticosterone levels after the first interaction. Chronic stress reduced sucrose consumption, which indicates anhedonia, in all the stressed groups. However, the PR subjects exhibited a longer immobility time and swam for less time than other subjects in the forced swim test (FST), and they travelled a shorter distance in the open field test (OFT). In this test, the ANA group also travelled smaller distances than the non-stressed group, but the difference was more moderate. In contrast, tumor development but not stress increased behaviors associated with anxiety in the OFT (e.g., time in the center) in all tumor-bearing subjects. In summary, although the effects of social stress and tumor development on behavior were rather moderate, the results indicate the importance of behavioral coping strategies in modulating the effects of chronic stress on health.

Sleep deprivation reduces the recovery of muscle injury induced by high-intensity exercise in a mouse model.

Sleep is crucial to improve athlete performance and their circadian rhythm, but sleep patterns may be disturbed because athletes participate in several competitions. In addition, intensive training programs can cause muscle pain and psychological stress in athletes, resulting in a lack of sleep. Sleep also plays a critical role in the recovery of muscle injury induced by exercise. The current study evaluated the effect of sleep deprivation on the recovery of muscle injury induced by high-intensity exercise in a mouse model. In this study, 28 mice were randomly assigned to four groups (N = 7): control (Control), exercise (EX), sleep deprivation (SD), and sleep deprivation with exercise (EX+SD). The mice from the EX and EX+SD groups were subjected to high-intensity swimming. The results showed that 72-h sleep deprivation increased food intake and reduced body weight. However, the manipulation of 8-week exercise and/or 72-h sleep deprivation did not have any effect in the elevated plus maze task and tail suspension test. Interestingly, the EX+SD group exhibited improved memory performance in the Morris water maze and impaired motor activity in the open field test. According to the TNF-α level and aspartate aminotransferase (AST), and creatine phosphokinase (CK) activities, only the EX+SD group exhibited muscle impairment. Overall, high-intensity exercise may cause muscle injury, and adequate sleep can recover muscle damage. However, sleep deprivation reduces protein synthesis, which decreases the ability to restore muscle damage and aggravates the harmful effect of high-intensity exercise.

Blockade of nicotinic acetylcholine receptor enhances the responsiveness to bupropion in the mouse forced swim test.

The objective of the present study is to investigate the role of α4, α5, α6 or ß2 nAChR subunits in the antidepressant-like effect of bupropion. Adult male mice were treated with subcutaneous acute doses of bupropion (3 and 10 mg/kg) 30 min before the forced swim test (FST) in α4, α5, α6, or ß2 nAChR subunit knockout (KO) and wild-type (WT) mice. In addition, the effects of ß2* antagonist dihydro-ß-erythroidine (DHßE, 3 mg/kg) on antidepressant-like effects of bupropion in C57BL/6 J mice were assessed. Our results showed that baseline immobility and climbing time did not differ between KO and corresponding WT mice except for ß2 KO. Bupropion significantly decreased immobility time and increased climbing time in the α4, α6 and ß2 nAChR KO mice in comparison to WT littermates, indicating that lack of these nAChR subunits enhanced antidepressant effects of bupropion. On the contrary, the α5 nAChR subunit deletion did not alter the FST behavior in the bupropion-treated mice. Not only in the transgenic mice, bupropion also showed antidepressant-like effects in the WT mice. In addition, DHßE pretreatment before bupropion administration resulted in decreased immobility time and increased climbing time. Taken together, the present study provides evidence on the involvement of α4*, α6*, and ß2* (* indicates possible presence of other subunits) nAChRs in the antidepressant-like effects of bupropion in the FST.

Influence of sex and estrous cycle on blood glucose levels, body weight gain, and depressive-like behavior in streptozotocin-induced diabetic rats.

Depression is the most common psychiatric disorder in diabetic patients, showing higher rates in women than in men. This comorbidity has been studied in rodents using the streptozotocin (STZ)-induced diabetes (DM) model, consistently reporting a depressive-like profile in males. Few articles have examined these disturbances in females (ovariectomized or combined with male rats) yielding controversial results. This work was aimed to study whether there are sex differences in the depressive-like profile of STZ-treated male and naturally cycling female Wistar rats. We also analyzed the possible influence of the estrous cycle in females. DM was induced by injecting STZ (50 mg/kg, i.p.) in 2 consecutive days. Ten days later, the depressive-like profile was assessed in the Forced-Swim Test (FST). Locomotion and motor coordination were also evaluated. Body weight and blood glucose levels were registered at the beginning and at the end of the experiment; the estrous cycle, food and water intake were daily monitored. All diabetic subjects showed increased blood glucose levels, polyphagia, polydipsia and decreased body weight as compared to controls, but males were more susceptible to STZ-treatment than females pooled in all phases of the estrous cycle. After treatment with STZ, males and females in proestrus/estrus (P/E) exhibited a depressive-like profile in the FST (increased immobility and reduced swimming); females in metestrus/diestrus were unaffected. The only sex difference observed was a more pronounced reduced swimming in STZ-treated P/E females compared with hyperglycemic males. No changes in locomotion or motor coordination were found. This work emphasizes estrous cycle differences in STZ-treated rats, and in the resultant depressive-like profile. It also supports clinical evidences made in women with DM and stresses the importance of studying STZ-treated naturally cycling females and their estrous cycle phases.

Avaliação da imobilidade tônica em codornas de corte via análise de sobrevivência' / Tonic immobility evaluation in meat quail via survival analysis

Tonic immobility (TI) is a way to measure fear, as characterized by the reduced capacity to respond to external stimuli. The time spent in TI indicates the level of fear. Since TI is measured as the time until event occurrence, survival analysis stands out as a suitable statistical method to treat these data. We aimed to investigate the influence of possible factors (lines, sex and age) on fear behavior in meat quail (Coturnix coturnix) measured through TI by using survival analysis (non parametric Kaplan-Meyer method via logrank test). The dataset was composed by TI information provided by 50 animals from each line (UFV1 and UFV2) in each age (14 and 28 days of age), totalizing 200 records. Despite the slight difference between the two evaluated ages, there was no significance for this factor between each studied line, UFV1 (P= 0.1493) and UFV2 (P= 0.2583). The logrank test indicated significant difference (P= 0.0407) between levels of line/sex groups at 14 days of age. We noted that males from UFV2 line presented higher fear behavior in relation to males from UFV1 line. No significant differences were observed for this factor when considering 28 days of age.(AU)

Predator odor evokes sex-independent stress responses in male and female Wistar rats and reduces phosphorylation of cyclic-adenosine monophosphate response element binding protein in the male, but not the female hippocampus.

Post-traumatic stress disorder (PTSD) is characterized by memory disturbances following trauma. Acute predator threat has emerged as an ethological model of PTSD, yet the effects of predator odor on signaling cascades associated with long-term memory remain poorly understood. In this study, we exposed male and female Wistar rats to the synthetic predator odor 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) to assess behavioral and physiological responses as well as rapid modulation of signal transduction cascades associated with learning and memory in the male and female hippocampus. During exposure to TMT in the homecage, both male and female animals displayed robust immobility, avoidance, and altered activity as a function of time. Physiologically, TMT exposure increased circulating corticosterone and blood glucose in both male and female rodents, suggesting that TMT evokes sex-independent behavioral and physiological responses. With respect to signal transduction, TMT exposure rapidly reduced phosphorylation of cyclic-adenosine monophosphate response element binding protein (CREB) in the male, but not the female hippocampus. Furthermore, TMT exposure reduced phosphorylation of extracellular signal-regulated kinase 1/2 and increased nuclear expression of the synapto-nuclear messenger protein Jacob in the male hippocampus, consistent with activation of the CREB shut-off pathway. In a follow-up behavioral experiment, post-training exposure to TMT did not affect spatial water maze performance of male rats. However, male rats re-introduced to the context in which TMT had previously been presented displayed avoidance and hyperactivity, but not freezing behavior or elevated corticosterone responses, suggesting that TMT exposure supports a form of contextual conditioning which is not characterized by immobility. Taken together, our findings suggest that TMT evokes similar behavioral and physiological responses in male and female Wistar rats, but affects distinct signaling cascades in the male and female hippocampus which may contribute to behavioral disruptions associated with predator exposure.

Later Life Changes in Hippocampal Neurogenesis and Behavioral Functions After Low-Dose Prenatal Irradiation at Early Organogenesis Stage.

PURPOSE: To investigate long-term changes in behavioral functions of mice after exposure to low-dose prenatal radiation at an early organogenesis stage. METHODS AND MATERIALS: Pregnant C57BL/6J mice were irradiated (20 cGy) at postcoitus day 5.5. The male and female offspring were subjected to different behavioral assays for affective, motor, and cognitive functions at 3, 6, and 12 months of age. Behavioral functions were further correlated with the population of CA1 and CA3 pyramidal neurons and immature neurons in hippocampal dentate gyrus. RESULTS: Prenatally exposed mice of different age groups showed a sex-specific pattern of sustained changes in behavioral functions. Male mice showed significant changes in anxiety-like phenotypes, learning, and long-term memory at age 3 months. At 6 months of age such behavioral functions were recovered to a normal level but could not be sustained at age 12 months. Female mice showed an appreciable recovery in almost all behavioral functions at 12 months. Patterns of change in learning and long-term memory were comparable to the population of CA1 and CA3 pyramidal neurons and doublecortin-positive neurons in hippocampus. CONCLUSION: Our finding suggests that prenatal (early organogenesis stage) irradiation even at a lower dose level (20 cGy) is sufficient to cause potential changes in neurobehavioral function at later stages of life. Male mice showed relatively higher vulnerability to radiation-induced neurobehavioral changes as compared with female.

The mesencephalic GCt-ICo complex and tonic immobility in pigeons (Columba livia): a c-Fos study.

Tonic immobility (TI) is a response to a predator attack, or other inescapable danger, characterized by immobility, analgesia and unresponsiveness to external stimuli. In mammals, the periaqueductal gray (PAG) and deep tectal regions control the expression of TI as well as other defensive behaviors. In birds, little is known about the mesencephalic circuitry involved in the control of TI. Here, adult pigeons (both sex, n = 4/group), randomly assigned to non-handled, handled or TI groups, were killed 90 min after manipulations and the brains processed for detection of c-Fos immunoreactive cells (c-Fos-ir, marker for neural activity) in the mesencephalic central gray (GCt) and the adjacent nucleus intercollicularis (ICo). The NADPH-diaphorase staining delineated the boundaries of the sub nuclei in the ICo-GCt complex. Compared to non-handled, TI (but not handling) induced c-Fos-ir in NADPH-diaphorase-rich and -poor regions. After TI, the number of c-Fos-ir increased in the caudal and intermediate areas of the ICo (but not in the GCt), throughout the rostrocaudal axis of the dorsal stratum griseum periventriculare (SGPd) of the optic tectum and in the n. mesencephalicus lateralis pars dorsalis (MLd), which is part of the ascending auditory pathway. These data suggest that inescapable threatening stimuli such as TI may recruit neurons in discrete areas of ICo-GCt complex, deep tectal layer and in ascending auditory circuits that may control the expression of defensive behaviors in pigeons. Additionally, data indicate that the contiguous deep tectal SCPd (but not GCt) in birds may be functionally comparable to the mammalian dorsal PAG.

Differential stress induced c-Fos expression and identification of region-specific miRNA-mRNA networks in the dorsal raphe and amygdala of high-responder/low-responder rats.

Chronic stress triggers a variety of physical and mental health problems, and how individuals cope with stress influences risk for emotional disorders. To investigate molecular mechanisms underlying distinct stress coping styles, we utilized rats that were selectively-bred for differences in emotionality and stress reactivity. We show that high novelty responding (HR) rats readily bury a shock probe in the defensive burying test, a measure of proactive stress coping behavior, while low novelty responding (LR) rats exhibit enhanced immobility, a measure of reactive coping. Shock exposure in the defensive burying test elicited greater activation of HR rats' caudal dorsal raphe serotonergic cells compared to LRs, but lead to more pronounced activation throughout LRs' amygdala (lateral, basolateral, central, and basomedial nuclei) compared to HRs. RNA-sequencing revealed 271 mRNA transcripts and 33 microRNA species that were differentially expressed in HR/LR raphe and amygdala. We mapped potential microRNA-mRNA networks by correlating and clustering mRNA and microRNA expression and identified networks that differed in either the HR/LR dorsal raphe or amygdala. A dorsal raphe network linked three microRNAs which were down-regulated in LRs (miR-206-3p, miR-3559-5p, and miR-378a-3p) to repression of genes related to microglia and immune response (Cd74, Cyth4, Nckap1l, and Rac2), the genes themselves were up-regulated in LR dorsal raphe. In the amygdala, another network linked miR-124-5p, miR-146a-5p, miR-3068-3p, miR-380-5p, miR-539-3p, and miR-7a-1-3p with repression of chromatin remodeling-related genes (Cenpk, Cenpq, Itgb3bp, and Mis18a). Overall this work highlights potential drivers of gene-networks and downstream molecular pathways within the raphe and amygdala that contribute to individual differences in stress coping styles and stress vulnerabilities.

A2 noradrenergic neurons regulate forced swim test immobility.

The Wistar-Kyoto (WKY) rat is a widely used animal model of depression, which is characterized by dysregulation of noradrenergic signaling. We previously demonstrated that WKY rats show a unique behavioral profile on the forced swim test (FST), characterized by high levels of immobility upon initial exposure and a greater learning-like response by further increasing immobility upon re-exposure than the genetically related Wistar rats. In the current study we aimed to determine whether altered activation of brainstem noradrenergic cell groups contributes to this behavioral profile. We exposed WKY and Wistar rats, to either 5min of forced swim or to the standard two-day FST (i.e. 15min forced swim on Day 1, followed by 5min on Day 2). We then stained their brains for FOS/tyrosine hydroxylase double-immunocytochemistry to determine potential differences in the activation of the brainstem noradrenergic cell groups. We detected a relative hyperactivation in the locus coeruleus of WKY rats when compared to Wistars in response to both one- and two-day forced swim. In contrast, within the A2 noradrenergic cell group, WKY rats exhibited diminished levels of FOS across both days of the FST, suggesting their lesser activation. We followed up these observations by selectively lesioning the A2 neurons, using anti-dopamine-ß-hydroxylase-conjugated saporin, in Wistar rats, which resulted in increased FST immobility on both days of the test. Together these data indicate that the A2 noradrenergic cell group regulates FST behavior, and that its hypoactivation may contribute to the unique behavioral phenotype of WKY rats.

Antidepressant actions of lateral habenula deep brain stimulation differentially correlate with CaMKII/GSK3/AMPK signaling locally and in the infralimbic cortex.

High frequency deep brain stimulation (DBS) of the lateral habenula (LHb) reduces symptoms of depression in severely treatment-resistant individuals. Despite the observed therapeutic effects, the molecular underpinnings of DBS are poorly understood. This study investigated the efficacy of high frequency LHb DBS (130Hz; 200µA; 90µs) in an animal model of tricyclic antidepressant resistance. Further, we reported DBS mediated changes in Ca(2+)/calmodulin-dependent protein kinase (CaMKIIα/ß), glycogen synthase kinase 3 (GSK3α/ß) and AMP-activated protein kinase (AMPK) both locally and in the infralimbic cortex (IL). Protein expressions were then correlated to immobility time during the forced swim test (FST). Antidepressant actions were quantified via FST. Treatment groups comprised of animals treated with adrenocorticotropic hormone alone (ACTH; 100µg/day, 14days, n=7), ACTH with active DBS (n=7), sham DBS (n=8), surgery only (n=8) or control (n=8). Active DBS significantly reduced immobility in ACTH-treated animals (p<0.05). For this group, western blot results demonstrated phosphorylation status of LHb CaMKIIα/ß and GSK3α/ß significantly correlated to immobility time in the FST. Concurrently, we observed phosphorylation status of CaMKIIα/ß, GSK3α/ß, and AMPK in the IL to be negatively correlated with antidepressant actions of DBS. These findings suggest that activity dependent phosphorylation of CaMKIIα/ß, and GSK3α/ß in the LHb together with the downregulation of CaMKIIα/ß, GSK3α/ß, and AMPK in the IL, contribute to the antidepressant actions of DBS.

Vasovagal syncope in humans and protective reactions in animals.

Vasovagal syncope (VVS) is not known to occur in animals, although other similar reflex responses are common. This review examines the possible relation of these latter presumably protective reflexes in animals to VVS in humans. The goal is to provide practitioners, and ultimately their patients, a meaningful understanding of the origins and appropriate management of this unpredictable affliction. This report utilized review of computer databases (e.g. PubMed) addressing VVS pathophysiology and origins, spontaneous transient loss of consciousness in animals, and comparative physiology. We also examined articles cited in the publications obtained by computer search and others suggested by colleagues. Articles were chosen based on those providing original observations and/or suggestions of novel mechanisms. In animals self-preservation is directed towards protection of the body through an escalation of behaviours depending on severity and proximity to danger. In humans self-preservation is directed not only to protection of the body, but also to protection of the brain's functional integrity. By virtue of loss of postural tone, the faint causes the body to assume a gravitationally neutral position, thereby offering a better chance of restoring brain blood supply and preserving brain function. Vasovagal syncope may seem to be a disadvantageous evolutionary adaptation. However, it is a reversible condition, that while exposing risk of injury and embarrassment, ultimately favours brain self-preservation in potentially threatening circumstances.

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 1 week prior to experimentation then randomly assigned to one of six conditions (Day 1 (15 min)/Day 2 (5 min)): (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.

Evidences for the agmatine involvement in antidepressant like effect of bupropion in mouse forced swim test.

Although bupropion has been widely used in the treatment of depression, the precise mechanism of its therapeutic actions is not fully understood. The present study investigated the role of agmatine in an antidepressant like effect of bupropion in mouse forced swim test. The antidepressant like effect of bupropion was potentiated by pretreatment with agmatine (10-20mg/kg, ip) and by the drugs known to increase endogenous agmatine levels in brain viz., l-arginine (40 µg/mouse, icv), an agmatine biosynthetic precursor, ornithine decarboxylase inhibitor, dl-α-difluoromethyl ornithine hydrochloride, DFMO (12.5 µg/mouse, icv), diamine oxidase inhibitor, aminoguanidine (6.5 µg/mouse, icv) and agmatinase inhibitor, arcaine (50 µg/mouse, icv) as well as imidazoline I1 receptor agonists, moxonidine (0.25mg/kg, ip) and clonidine (0.015 mg/kg, ip) and imidazoline I2 receptor agonist, 2-(2-benzofuranyl)-2-imidazoline hydrochloride, 2-BFI (5mg/kg, ip). Conversely, prior administration of I1 receptor antagonist, efaroxan (1mg/kg, ip) and I2 receptor antagonist, idazoxan (0.25mg/kg, ip) blocked the antidepressant like effect of bupropion and its synergistic combination with agmatine. These results demonstrate involvement of agmatine in the antidepressant like effect of bupropion and suggest agmatine and imidazoline receptors as a potential therapeutic target for the treatment of depressive disorders.

The functional role of ascending nociceptive control in defensive behavior.

Ascending nociceptive control is a novel spino-striato-rostral ventral medulla pain modulation pathway that mediates heterosegmental pain-induced analgesia, i.e., noxious stimulus-induced antinociception. In this study, we used the dorsal immobility response in rats as a model of the defensive responses. We demonstrated that the activation of ascending nociceptive control by peripheral noxious stimulation and spinal AMPA and mGluR1 receptor blockade significantly potentiated the duration of the dorsal immobility response in rats via an opioid-dependent mechanism in the nucleus accumbens. These results demonstrated the functional role of ascending nociceptive control in the modulation of defensive responses and spinal glutamatergic receptors in the dorsal immobility response. The immobility response is an antipredator behavior that reflects the underlying state of fear, and ascending nociceptive control may modulate fear.

Peritraumatic tonic immobility is associated with posttraumatic stress symptoms in undergraduate Brazilian students / A imobilidade tônica peritraumática está associada aos sintomas do transtorno de estresse pós-traumático em estudantes brasileiros de graduação

OBJECTIVE: Tonic immobility is a defensive reaction occurring under extreme life threats. Patients with posttraumatic stress disorder (PTSD) reporting peritraumatic tonic immobility show the most severe symptoms and a poorer response to treatment. This study investigated the predictive falue of tonic immobility for posttraumatic stress symptoms in a non-clinical sample. METHODS: One hundred and ninety-eight college students exposed to various life threatening events were selected to participate. The Posttraumatic Stress Disorder Checklist - Civilian Version (PCL-C) and tonic immobility questions were used. Linear regression models were fitted to investigate the association between peritraumatic tonic immobility and PCL-C scores. Peritraumatic dissociation, peritraumatic panic reactions, negative affect, gender, type of trauma, and time since trauma were considered as confounding variables. RESULTS: We found significant association between peritraumatic tonic immobility and PTSD symptoms in a non-clinical sample exposed to various traumas, even after regression controlled for confounding variables (β = 1.99, p = 0.017). CONCLUSIONS: This automatic reaction under extreme life threatening stress, although adaptive for defense, may have pathological consequences as implied by its association with PTSD symptoms.

OBJETIVO: A imobilidade tônica é uma resposta defensiva que ocorre sob ameaça extrema à vida. Pacientes com transtorno de estresse pós-traumático (TEPT) que relatam imobilidade tônica peritraumática são os que apresentam os sintomas mais graves e a pior resposta ao tratamento. Este estudo investigou o valor preditivo da imobilidade tônica para os sintomas de TEPT em uma amostra não clínica. MÉTODOS: Os participantes da pesquisa foram 198 estudantes universitários expostos a traumas diversos. A versão brasileira do Post-Traumatic Stress Disorder Checklist Civilian Version (PCL-C) e questões referentes à imobilidade tônica foram empregadas. Modelos de regressão linear foram utilizados para investigar a associação dos sintomas de estresse pós-traumático com a imobilidade tônica peritraumática. Foram consideradas como variáveis de confusão a dissociação peritraumática, as reações físicas de pânico peritraumática, o traço de afeto negativo, o gênero, o tipo de trauma e o tempo de trauma. RESULTADOS: Encontrou-se uma associação significativa entre a imobilidade tônica peritraumática e os sintomas de TEPT em uma amostra não clínica exposta a traumas diversos mesmo quando controlada por variáveis de confusão (β = 1,99; p = 0,017). CONCLUSÕES: Esta reação defensiva que ocorre sob intensa ameaça, apesar de adaptativa para a defesa, pode ter consequências patológicas como sugere sua associação aos sintomas de TEPT.

Comparison of the effects of estradiol and progesterone on serotonergic function.

BACKGROUND: Ovarian hormones may contribute to the vulnerability to depression, as well as to the response to antidepressants (ADs). Previously, we reported that acute systemic treatment with estradiol or progesterone blocked the ability of the selective serotonin reuptake inhibitor, fluvoxamine, to inhibit serotonin transporter function in ovariectomized rats. In this study, behavioral consequences, as well as receptor mechanisms underlying these hormonal effects, were investigated. METHODS: Using the forced swimming test, the acute effect of estradiol and/or progesterone on fluvoxamine's AD-like effects was investigated. Using in vivo chronoamperometry, the effect of local application of estradiol or progesterone into the hippocampus of ovariectomized rats on serotonin (5-HT) clearance, as well as on the ability of fluvoxamine to slow 5-HT clearance, were investigated. RESULTS: The decreased immobility and increased swimming caused by fluvoxamine in the forced swimming test was blocked in rats treated with estradiol and/or progesterone. Local application of estradiol, but not progesterone, slowed 5-HT clearance and both hormones blocked the ability of fluvoxamine to slow 5-HT clearance. Use of hormone receptor agonists and antagonists, revealed that the effects of estradiol are mediated by activation of membrane, as well as nuclear estrogen receptors (ER). The AD-like effect of estradiol involved ER beta and G-protein coupled receptor 30, whereas its blockade of fluvoxamine's effects was ER alpha-mediated. The effects of progesterone occurred solely by activation of intracellular progesterone receptors. CONCLUSIONS: Targeting of ER beta or G-protein coupled receptor 30 might reveal a strategy to permit beneficial effects of estrogen without its deleterious effect on selective serotonin reuptake inhibitor efficacy.

Estrogen effects on the forced swim test differ in two outbred rat strains.

Changes in reproductive hormones, such as estrogen, play a role in mood regulation. The present study examined strain differences (Long-Evans vs. Wistar-Hannover) in the behavioral and biochemical effects of estrogen manipulation. Adult ovariectomized female rats were treated with estradiol, vehicle, or withdrawn from estradiol. The two strains demonstrated differential behavioral responses to short-term estradiol administration in the forced swim test; estradiol induced an antidepressant-like effect in Long-Evans rats but not in Wistar rats. Conversely, withdrawal from estradiol resulted in a depressive-like state in the Wistar rats but not in the Long-Evans rats. Western blot analyses found no differences in estrogen receptors α and ß within the hippocampus or the frontal cortex, two brain areas strongly implicated in affective disorders. These data demonstrate the importance of strain as a variable when interpreting behavioral effects of estrogen.

Cognitive impairments in adult mice with constitutive inactivation of RIP140 gene expression.

Receptor-interacting protein 140 (RIP140) is a negative transcriptional coregulator of nuclear receptors such as estrogen, retinoic acid or glucocorticoid receptors. Recruitment of RIP140 results in an inhibition of target gene expression through different repressive domains interacting with histone deacetylases or C-terminal binding proteins. In this study, we analyzed the role of RIP140 activity in memory processes using RIP140-deficient transgenic mice. Although the RIP140 protein was clearly expressed in the brain (cortical and hippocampus areas), the morphological examination of RIP140(-/-) mouse brain failed to show grossly observable alterations. Using male 2-month-old RIP140(-/-) , RIP140(+/-) or RIP140(+/+) mice, we did not observe any significant differences in the open-field test, rotarod test and in terms of spontaneous alternation in the Y-maze. By contrast, RIP140(-/-) mice showed long-term memory deficits, with an absence of decrease in escape latencies when animals were tested using a fixed platform position procedure in the water maze and in the passive avoidance test. Noteworthy, RIP140(-/-) mice showed decreased swimming speed, suggesting swimming alterations that may in part account for the marked alterations measured in the water maze. Moreover, RIP140(+/-) and RIP140(-/-) mice showed a significant increase in immobility time in the forced swimming test as compared with wild-type animals. These observations showed that RIP140 gene depletion results in learning and memory deficits as well as stress response, bringing to light a major role for this transcriptional coregulator in the neurophysiological developmental mechanisms underlying cognitive functions.