AIMS:Prenatal alcohol exposure (PAE) is associated with Fetal Alcohol Spectrum Disorders (FASD), characterized by persistent cognitive, adaptive, and neurosensory impairments. Alcohol disrupts processes of cerebral development underlying multisensory integration and lateralization, which are essential for cognitive and behavioral functioning. This study used the Brief Multisensory Integration Battery (BMIB) and the Global Lateral Preference Inventory (GLPI) to detect FASD-related neurocognitive and sensory features. METHODS:Three adolescents with documented PAE were assessed with the BMIB and GLPI, alongside standardized neuropsychological tests and measures of physical development. Analyses focused on patterns of multisensory integration, lateral preference, and broader cognitive functioning as potential markers of FASD. RESULTS:All participants showed deficits in multisensory tasks and atypical lateralization across sensory and motor domains. These impairments aligned with known neurodevelopmental disruptions associated with PAE. The BMIB and GLPI demonstrated sensitivity in capturing clinically relevant dysfunctions. CONCLUSIONS:Findings provide preliminary evidence for the clinical utility of these tools in identifying PAE-related deficits. Early detection may improve diagnostic accuracy and guide targeted interventions. Larger studies are needed to confirm their psychometric robustness.

This study examines the complex interplay between social behavior and mental health, focusing on the neurobiological mechanisms underlying human interactions and their alterations associated with anxiety and depression disorders. These conditions are characterized by heightened threat perception, pervasive worry, physiological responses, emotional dysregulation, and maladaptive behaviors. Through narrative review, this study examines both aspects, addressing social isolation as both a risk factor and an avoidance behavior that may provide temporary relief but ultimately perpetuate the clinical condition in the long term. The findings offer valuable insights for clinical practice, emphasizing interventions that enhance cognitive flexibility to foster stable and supportive interpersonal relationships.

Background/Objectives Studies in rodents indicate that disruptions in both cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) signaling pathways are involved in the development of hyperactive behavior. We examined whether vinpocetine, a phosphodiesterase type 1 inhibitor that enhances brain cAMP and cGMP levels, could mitigate locomotor hyperactivity in mice exposed to lead during early development. Methods Swiss mice were exposed to 90 ppm of lead in their drinking water throughout gestation and the first ten postnatal days. At postnatal day 10 (PN10), blood lead levels (BLLs) were about 30 µg/dL. At PN30, animals either received vinpocetine (20 mg/kg, i.p.) or a vehicle 4 h before the evaluation of locomotor activity in the open field. Results Lead-exposed males did not display differences in locomotor activity compared to controls, while lead-exposed females showed a significant increase in locomotion. Vinpocetine treatment significantly reversed the lead-induced hyperactivity in females. Conclusions These findings suggest that the cAMP and cGMP signaling pathways play a role in the hyperactivity induced by lead exposure.

Eating disorders (ED) are severe psychiatric disorders characterized by dysfunctional behaviors related to eating or weight control, with profound impacts on health, quality of life, and the financial burden of affected individuals and society at large. Given that these disorders involve disturbances in self-perception, it is crucial to comprehend the role of self-awareness in their prevalence and maintenance. This literature review presents different self-awareness processes, discussing their functioning across different levels of complexity. By deconstructing this concept, we can gain a better understanding of how each facet of self and personality relates to the symptoms of these disorders. Understanding the absence or impairment of self-awareness in ED holds significant implications for diagnosis, treatment, and overall management. By recognizing and comprehending the characteristics of self-awareness, clinicians can develop tailored interventions and evidence-based treatments for individuals with ED. Furthermore, this narrative review underscores the importance of considering temperament and personality factors in the context of ED, as temperament traits and personality characteristics may interact with self-awareness processes, influencing the development and maintenance of ED. Ultimately, the results highlight the pressing need for further research on the development of effective interventions and support strategies grounded in the aspects of self-awareness mechanisms for individuals affected by these disorders.

This study investigated the impact of social isolation in Carioca High-Conditioned Freezing (CHF) rats, an animal model of generalized anxiety disorder (GAD). Animals selected for high (CHF), low trait anxiety (Carioca Low-Conditioned Freezing, CLF), and control rats from randomly bred populations (CTL) were housed in groups or kept isolated in their cages for 14 consecutive days. On the fifteenth day, all animals underwent the Forced Swimming Test (FST), where the latency to immobility was assessed as a depressive-like measure. Under standard grouping conditions, CHF rats showed a shorter latency to immobility in the FST compared to CTL and CLF animals, indicating depressive-like characteristics and possible GAD comorbidity. Social isolation decreased the latency to immobility in CLF and CTL animals, while it paradoxically increased this measure in CHF animals. Therefore, social isolation exerted a depressive-like action in CTL and CLF rats, but had a protective or "antidepressant-like" effect in CHF animals. Since, CHF rats are housed with other animals with high trait anxiety, such protective action induced by social isolation might have been due to the mitigation of what has been referred to as "social stress contagion". These results are discussed regarding the association between depressive-like behaviors and reduced social engagement.

Visual stimuli and limbic activation varyingly influence obsessive-compulsive symptom expression and so impact treatment outcomes. Some symptom phenotypes, for example, covert repugnant thoughts, are likely less sensitive to sensory stimuli compared to symptoms with an extrinsic focus, that is, symptoms related to contamination, safety, and "just-right-perceptions." Toward an improved understanding of the neurocognitive underpinnings of obsessive-compulsive psychobiology, work in naturalistic animal model systems is useful. Here, we explored the impact of visual feedback and limbic processes on 24 normal (NNB) and large (LNB) nesting deer mice, respectively (as far as possible, equally distributed between sexes). Briefly, after behavioral classification into either the NNB or LNB cohorts, mice of each cohort were separated into two groups each and assessed for nesting expression under either standard light conditions or conditions of complete visual deprivation (VD). Nesting outcomes were assessed in terms of size and neatness. After nesting assessment completion, mice were euthanized, and samples of frontal-cortical and hippocampal tissues were collected to determine serotonin and noradrenaline concentrations. Our results show that LNB, as opposed to NNB, represents an inflexible and excessive behavioral phenotype that is not dependent on visually guided action-outcome processing, and that it associates with increased frontal-cortical and hippocampal noradrenaline concentrations, irrespective of lighting condition. Collectively, the current results are informing of the neurocognitive underpinnings of nesting behavior. It also provides a valuable foundation for continued investigations into the noradrenergic mechanisms that may influence the development and promulgation of excessive, rigid, and inflexible behaviors. Visual stimuli and limbic activation varyingly influence obsessive-compulsive symptoms. We explored the impact of visual feedback and limbic processes on normal (NNB) and large (LNB) nesting deer mice. Nesting outcomes were assessed in terms of size and neatness, while limbic activation was measured by means of frontal-cortical and hippocampal serotonin and noradrenaline analyses. We found that LNB, as opposed to NNB, is inflexible and excessive and is not dependent on visually guided feedback. It also associates with increased frontal-cortical and hippocampal noradrenaline concentrations.image

Exposure to substances of abuse during pregnancy can have long-lasting effects on offspring. Alcohol is one of the most widely used substances of abuse that leads to the most severe consequences. Recent studies in the United States, Canada, and the United Kingdom showed that between 1% and 7% of all children exhibit signs and symptoms of fetal alcohol spectrum disorder (FASD). Despite preventive campaigns, the rate of children with FASD has not decreased during recent decades. Alcohol consumption often accompanies exposure to such drugs as tobacco, cocaine, opioids, and cannabis. These interactions can be synergistic and exacerbate the deleterious consequences of developmental alcohol exposure. The present review focuses on interactions between alcohol and cannabis exposure and the potential consequences of these interactions.

The Carioca rat lines originated from the selective bidirectional breeding of mates displaying extreme defense responses to contextual conditioned fear. After three generations, two distinct populations could be distinguished: the Carioca High- and Low-conditioned Freezing rats, CHF, and CLF, respectively. Later studies identified strong anxiety-like behaviors in the CHF line, while indications of impulsivity and hyperactivity were prominent in the CLF animals. The present review details the physiological and pharmacological-related findings obtained from these lines. The results discussed here point towards a dysfunctional fear circuitry in CHF rats, including alterations in key brain structures and the serotoninergic system. Moreover, data from these animals highlight important alterations in the stress-processing machinery and its associated systems, such as energy metabolism and antioxidative defense. Finally, evidence of an alteration in the dopaminergic pathway in CLF rats is also debated. Thus, accumulating data gathered over the years, place the Carioca lines as significant animal models for the study of psychiatric disorders, especially fear-related ones like anxiety.

The COVID-19 pandemic has placed unprecedented burdens on individuals and communities around the world. The isolation, fear, and uncertainty caused by the virus has led to increased rates of anxiety, depression, and other mental health issues. The pandemic has also had a disproportionate impact on individuals and communities with low income and socioeconomic status.ObjectiveTo shed light on the consequences of the pandemic on individuals from minorities and low-income areas, we investigate the main reasons that led patients who were referred to a social clinic of a private university in Rio de Janeiro to seek psychological treatment before (2019) and during the pandemic (2020 and 2021).MethodsWe conducted a quanti-qualitative study with a lexical analysis that evaluated 549 complaint forms of patients seeking treatment in these two distinct periods. Our analyses included descending hierarchical analysis (DHA) and correspondence factor analysis (CFA).ResultsFamily dynamics and communication factors play a dominant role in the reason for seeking therapy and psychological treatment. Additionally, our study suggested an increase in anxiety and panic attacks among other mental health issues associated with grief and losses during the pandemic years.ConclusionBased on these analyses, we can begin to identify a few changes in the main demand and redirection of complaints of patients during the period of COVID-19.

The participation of the hippocampal formation in consolidation and reconsolidation of contextual fear memories has been widely recognized and known to be dependent on the activation of the cAMP response element (CRE) binding protein (CREB) pathway. Recent findings have challenged the prevailing view that over time contextual fear memories migrate to neocortical circuits and no longer require the hippocampus for retrieval of remote fearful memories. It has also recently been found that this brain structure is important for the maintenance and recall of remote fear memories associated with aversive events, a common trait in stress-related disorders such as generalized anxiety disorder (GAD), major depression, and post-traumatic stress disorder. In view of these findings, here we examined the putative role of CREB in the hippocampus of an animal model of GAD during the retrieval of remote contextual fear memories. Specifically, we evaluated CREB phosphorylation in the hippocampus of male Carioca High- and Low-conditioned Freezing rats (CHF and CLF, respectively) upon re-exposure of animals to contextual cues associated to footshocks weeks after fear conditioning. Age-matched male rats from a randomized crossbreeding population served as controls (CTL). Adrenal catecholamine levels were also measured as a biological marker of stress response. Seven weeks after contextual fear conditioning, half of the sample of CHF (n = 9), CLF (n = 10) and CTL (n = 10) rats were randomly assigned to return to the same context chamber where footshocks were previously administrated (Context condition), while the remaining animals were individually placed in standard housing cages (Control condition). Western blot results indicated that pCREB levels were significantly increased in the hippocampus of CHF rats for both Context and Control conditions when compared to the other experimental groups. CHF rats in the Context condition also exhibited significant more freezing than that observed for both CLF and CTL rats. Lastly, CHF animals in the Context condition displayed significantly higher adrenal catecholamine levels than those in the Control condition, whereas no differences in catecholamine levels were observed between Context and Control conditions for CLF and CTL rats. These findings are discussed from a perspective in which the hippocampus plays a role in the maintenance and recall of remote contextual fear memories via the CREB pathway.

Glioblastoma is the most invasive and malignant brain tumor, for which no effective treatment is currently available. Heat shock protein 90 (HSP90) is a potential target for the treatment of different types of cancer. Herein, we investigated the effect of gedunin, an HSP90 inhibitor, in murine GL261 glioblastoma in vitro and in vivo models. Gedunin treatment decreased GL261 cell proliferation and triggered apoptosis in a concentration- dependent manner. Gedunin also reduced GL261 cell migration and metalloproteinase-2 activity, suggesting that it impairs glioblastoma cell invasion. Despite the reduction of total protein content in gedunin-treated cells, the phosphorylation of STAT3 and ERK1/2 pathways was enhanced within 24 h. In situ treatment with gedunin did not significantly reduce tumor volume but reduced the presence of vascular structures in xenograft glioblastoma in C57BL/6 mice, a clinical feature associated with morbidity and mortality. Our results demonstrate that gedunin is a promising compound for the treatment of glioblastoma. ![Figure][1] Highlights ### Competing Interest Statement The authors have declared no competing interest. [1]: pending:yes

Obsessive-compulsive disorder (OCD) is characterized by recurring obsessive thoughts and repetitive behaviors that are often associated with anxiety and perturbations in cortico-striatal signaling. Given the suboptimal response of OCD to current serotonergic interventions, there is a need to better understand the psychobiological mechanisms that may underlie the disorder. In this regard, investigations into adenosinergic processes might be fruitful. Indeed, adenosine modulates both anxiety- and motor behavioral output. Thus, we aimed to explore the potential associations between compulsive-like large nest building (LNB) behavior in deer mice, anxiety and adenosinergic processes. From an initial pool of 120 adult deer mice, 34 normal nest building (NNB)- and 32 LNB-expressing mice of both sexes were selected and exposed to either a normal water (wCTRL) or vehicle control (vCTRL), lorazepam (LOR) or istradefylline (ISTRA) for 7- (LOR) or 28 days after which nesting assessment was repeated and animals screened for anxiety-like behavior in an anxiogenic open field. Mice were then euthanized, the striatal tissue removed on ice and the adenosine A2A receptor expression quantified. Our findings indicate that NNB and LNB behavior are not distinctly associated with measures of generalized anxiety and that ISTRA-induced changes in nesting expression are dissociated from changes in anxiety scores. Further, data from this investigation show that nesting in deer mice is directly related to striatal adenosine signaling, and that LNB is founded upon a lower degree of adenosinergic A2A stimulation.

Fetal Alcohol Spectrum Disorder (FASD) is a collective name for lifelong physical and neurodevelopmental problems caused by the gestational consumption of alcohol affecting fetal development. In Brazil, the lack of awareness among healthcare professionals, and the scarcity of suitable diagnostic tools and trained clinicians, can contribute to the underestimation of FASD prevalence and severity. The present review aims to map and analyze studies conducted in Brazil on children and adolescents with FASD or a history of prenatal alcohol exposure (PAE). Additionally, it intends to report the psychometric properties of the neurodevelopmental assessment tools applied in the selected articles. Searches were carried out in the databases Scielo, LILACS, PePSIC, EMBASE, PsycINFO, Web of Science, selecting original clinical studies that have investigated the neurodevelopment of this population. From a total of 175 studies, ten articles fit the inclusion criteria in which 18 instruments were identified. The most reported deficits were related to language, general intelligence quotient (IQ), adaptive behavior, attention, and visual perception. Our results point to the need for more clinical research on FASD in Brazil, as well as for the standardization and validation of neurodevelopmental assessment tools for the accurate diagnosis of FASD in Brazil.

Stress and eating disorders are closely related and are a topic of major concern due to their burden on human health. Engaging in unhealthy eating habits may come as a result of stress, and it often serves to alleviate the symptoms of anxiety or as a distraction from the stressor itself or self-awareness. However, it can also lead to negative feelings of a person's body figure, guilty, or shame. As diverse as these consequences are in humans, so are the effects of the combined administration of stress and hypercaloric food in animals' models. In this study, we assessed the influence of individual innate behavioral predisposition on the effects of chronic unpredictable mild stress and the dietary supplementation with high-sugar/high-fat food. These conditions were applied to male Carioca low- and high-conditioned freezing (CLF and CHF) rats for 21 days. Behavioral results show that the hypercaloric supplement had a protective effect over the alterations caused by the stress. Notably, it was more strongly observed in CHF rather than CLF animals. As the chronic stress led to an impaired behavior in the contextual fear conditioning and the forced swimming tests in the CLF line, animals fed with the HSHF pellet scored responses similar to their untreated control. On CHF rats, these effects also were seen to a broader extent on the open field test, where the locomotor behavior was also increased. No major effects of the diet were seen in the unstressed groups. Overall, our results show that the influences of both chronic stress and hypercaloric feeding depend on innate differences in fear response traits of male Carioca rats.

Chronic-stress-induced depression is recognized as a widespread public health concern. Selective serotonin reuptake inhibitors (SSRIs) have been the most common treatment for this illness. However, the role of 5-hydroxytryptamine (5-HT) receptor subtypes in stress-induced depression remains unclear. Evidence from Animal studies has reported a variety of results regarding the effects of chronic unpredictable mild stress (CUMS) on serotonin signaling pathways and 5-HT receptor subtypes. This divergence may rely on differences in protocols, methods, and studied pathways. Thus, the aim of this systematic review was to weigh the currently available findings regarding serotonin receptor changes in animal models of CUMS. Overall, our meta-analysis results showed the association of altered expression of 5-HT1A receptors in the frontal cortex and 5-HT2A receptors both in the whole cortex and the hypothalamus of rats following CUMS. Moreover, by using a qualitative-structured analysis and the application of risk-of-bias tools, we identified possible sources of data variation between the studied literature, which should be taken into account in future animal studies of chronic-stress induced depression.

Anxiety is characterized as the emotional response in anticipation of a future threat. This hypervigilant state comprehends a cascade of neuroendocrine and physiological processes, involving the renin-angiotensin system (RAS) and hypothalamic-pituitary-adrenal axis (HPA). Excessive and chronic anxiety may ultimately lead to the development of anxiety disorders. This systematic review aimed to investigate experimental studies using animal models that explored the relationship between RAS and the HPA axis in anxiety disorders. A systematic search was conducted in MEDLINE/PubMed, Embase and Web of Science, and was performed according to PRISMA guidelines. The inclusion criteria was mainly the mention of RAS, HPA axis, and an anxiety disorder in the same study. Quality of studies was evaluated according to the table of risk of bias from SYRCLE. From 12 eligible studies, 7 were included. Research in rats and mice shows that the overactivation of the RAS and HPA axis triggers several neuroendocrine reactions, mainly mediated by AT1 receptors, which promote anxiety-like behaviors and positive feedback for its hyperactivation. On the contrary, the administration of antihypertensive drugs, such as angiotensin AT1 receptor blocker, propitiated the regulation of the RAS and HPA axis, maintaining homeostasis even amid aversive situations. Assessment of risk of bias revealed a pronounced unclear to high risk in several categories, which thus jeopardize the comparability and reproducibility of the results. Nonetheless, the preclinical evidence indicates that the hyperactivation of both RAS and HPA axis during stress exerts deleterious consequences, inducing anxiogenic responses. Moreover, the compiled results show that the modulation of both systems by the administration of AT1 receptor blockers produce anxiolytic effects in animal models and may constitute a new venue for the treatment of anxiety-like disorders.

Chronic unpredictable mild stress (CUMS) is a widely used model to study stress-coping strategies in rodents. Different factors have been shown to influence whether animals adopt passive or active coping responses to CUMS. Individual adaptation and susceptibility to the environment seem to play a critical role in this process. To further investigate this relationship, we examined the effects of CUMS on Carioca high- and low-conditioned freezing rats (CHF and CLF, respectively), bidirectional lines of animals selected for high and low freezing in response to contextual cues that were previously associated with footshocks. For this purpose, the behavior of CHF and CLF animals was evaluated in the contextual fear conditioning, open field, elevated T maze, and forced swimming tests before and after 21 days of CUMS. For all tests, CHF rats were more susceptible to the effects of CUMS compared to CLF. CHF animals exposed to CUMS displayed a reduction in freezing behavior, decreased number of entries and time spent in the center of the open field, greater latencies to become immobile, and increased avoidance and escaping behaviors in the elevated T maze. Overall, these findings support the hypothesis that a heightened susceptibility to the environment exerts a strong influence on coping responses to chronic stress.