Impact of social isolation on the oxytocinergic system: A systematic review and meta-analysis of rodent data.

Social isolation (SI) stress results from a combination of intrinsic and environmental factors and is associated with a variety of negative developmental outcomes. Oxytocin (OXT) might play a role in the consequences of SI in the brain and periphery. We conducted a systematic review and meta-analysis to compile data about the effects of SI in the oxytocinergic system of rats and mice, and its relation to behavioral alterations. Five databases (EMBASE, PsychNet, PubMed, Scopus, and Web of Science) were searched in March 2021, using ("Social Isolation" AND (mouse OR rat) AND (oxytocin OR oxytocin receptor)). This review followed the PRISMA guidelines, including registration in PROSPERO, and risk of bias assessment. The twelve articles included in this review indicated that SI was associated with decreased OXTR levels, resulting in behavioral alterations like increased aggression and anxiety-like behavior, hyperactivity, and diminished social behaviors and memory. No significant effects on OXT levels were observed. Administration of synthetic OXT or its agonists partially decreases those unwanted behaviors to similar levels of control animals.

The costs of coping: Different strategies to deal with social defeat stress might come with distinct immunologic, neuroplastic, and oxidative stress consequences in male Wistar rats.

The impact of stress on health and well-being is determined by the ability of an individual to cope with challenges imposed by the stressor. Animals exposed to social defeat stress show different patterns of response during confrontations, leading to distinct stress-induced consequences. Using an established resident-intruder paradigm, we explored the outcomes of adopting active or passive coping strategies during a social defeat protocol over peripheral and central nervous system (CNS) levels of inflammatory cytokines, growth factors, glucocorticoid, and oxidative stress markers in male Wistar rats. Animals that presented short latency to assume a defeated posture during confrontation-considered as susceptible to stress-exhibited increased levels of brain-derived neurotrophic factor (BDNF) in the amygdala (AMY) and in the bed nucleus of the stria terminalis (BNST), and decreased lipid peroxidation in the CNS, suggesting changes in antioxidative defenses as well as stress-induced neuroadaptations. On the other hand, animals with longer latencies to assume a submissive posture-considered to be resilient to stress-presented lower levels of CNS BDNF compared to short-latency animals and decreased enzymatic antioxidant defenses in the CNS in comparison to controls, which might indicate an increased risk of central oxidative damage. From the results, behavioral reactivity cannot be considered a predictor of success in responding to stress; however, the findings of this study reinforce the idea that exposure to stress has no predetermined negative effects. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Corticotropin-releasing factor receptor signaling and modulation: implications for stress response and resilience.

Introduction In addition to their role in regulation of the hypothalamic-pituitary-adrenal-axis, corticotropin-releasing factor (CRF) and its related peptides, the urocortins, are important mediators of physiological and pathophysiological processes of the central nervous, cardiovascular, gastrointestinal, immune, endocrine, reproductive, and skin systems. Altered regulation of CRF-mediated adaptive responses to various stressful stimuli disrupts healthy function and might confer vulnerability to several disorders, including depression and anxiety. Methodology This narrative review was conducted through search and analysis of studies retrieved from online databases using a snowball method. Results This review covers aspects beginning with the discovery of CRF, CRF binding protein and their actions via interaction with CRF receptors type 1 and type 2. These are surface plasma membrane receptors, activation of which is associated with conformational changes and interaction with a variety of G-proteins and signaling pathways. We also reviewed the pharmacology and mechanisms of the receptor signaling modulatory activity of these receptors. Conclusion This review compiles and presents knowledge regarding the CRFergic system, including CRF related peptides, CRF binding protein, and CRF receptors, as well as some evidence that is potentially indicative of the biological roles of these entities in several physiological and pathophysiological processes.

Corticotropin-releasing factor receptor signaling and modulation: implications for stress response and resilience

Abstract Introduction In addition to their role in regulation of the hypothalamic-pituitary-adrenal-axis, corticotropin-releasing factor (CRF) and its related peptides, the urocortins, are important mediators of physiological and pathophysiological processes of the central nervous, cardiovascular, gastrointestinal, immune, endocrine, reproductive, and skin systems. Altered regulation of CRF-mediated adaptive responses to various stressful stimuli disrupts healthy function and might confer vulnerability to several disorders, including depression and anxiety. Methodology This narrative review was conducted through search and analysis of studies retrieved from online databases using a snowball method. Results This review covers aspects beginning with the discovery of CRF, CRF binding protein and their actions via interaction with CRF receptors type 1 and type 2. These are surface plasma membrane receptors, activation of which is associated with conformational changes and interaction with a variety of G-proteins and signaling pathways. We also reviewed the pharmacology and mechanisms of the receptor signaling modulatory activity of these receptors. Conclusion This review compiles and presents knowledge regarding the CRFergic system, including CRF related peptides, CRF binding protein, and CRF receptors, as well as some evidence that is potentially indicative of the biological roles of these entities in several physiological and pathophysiological processes.

Earlier Alcohol Use and Lower Neuropsychological Performance in Brazilian Adolescence: Is the School Environment Related to This?

OBJECTIVES: The aim of this study was to evaluate impulsivity, inhibitory control, and alcohol use in preadolescents and adolescents aged 10 to 16 from public and private schools. METHODS: Participants were 190 adolescents selected from public and private schools in Brazil. Neuropsychological measures related to impulsivity (i.e., Barratt Impulsiveness Scale), inhibitory control (i.e., Go/No-go Task), and processing speed (i.e., Five Digits Test) were assessed. RESULTS: 60% of the sample had started drinking alcohol. Early alcohol consumption is not influenced by type of school, indicating that adolescents consume alcohol early, regardless of the type of education or income. Although there were significant differences in neuropsychological performance between types of schools, better neuropsychological performance was found in students from private schools. CONCLUSIONS: When comparing consumption of alcohol among public and private school students, there were no significant differences, perhaps because the use of early alcohol can be a public health problem. Private school students may perform better in inhibitory control task because they have a good school environment, which serves as a protective factor.

Recovery of stress-impaired social behavior by an antagonist of the CRF binding protein, CRF6-33, in the bed nucleus of the stria terminalis of male rats.

Social stress is recognized to promote the development of neuropsychiatric and mood disorders. Corticotropin releasing factor (CRF) is an important neuropeptide activated by social stress, and it contributes to neural and behavioral adaptations, as indicated by impaired social interactions and anhedonic effects. Few studies have focused on the role of the CRF binding protein (CRFBP), a component of the CRF system, and its activity in the bed nucleus of stria terminalis (BNST), a limbic structure connecting amygdala and hypothalamus. In this study, animals' preference for sweet solutions was examined as an index of stress-induced anhedonic responses in Wistar rats subjected to four brief intermittent episodes of social defeat. Next, social approach was assessed after local infusions of the CRFBP antagonist, CRF fragment 6-33 (CRF6-33) into the BNST. The experience of brief episodes of social defeat impaired social approach behaviors in male rats. However, intra-BNST CRF6-33 infusions restored social approach in stressed animals to the levels of non-stressed rats. CRF6-33 acted selectively on social interaction and did not alter general exploration in nether stressed nor non-stressed rats. These findings suggest that BNST CRFBP is involved in the modulation of anxiety-like responses induced by social stress.

Social instigation and repeated aggressive confrontations in male Swiss mice: analysis of plasma corticosterone, CRF and BDNF levels in limbic brain areas.

INTRODUCTION:: Agonistic behaviors help to ensure survival, provide advantage in competition, and communicate social status. The resident-intruder paradigm, an animal model based on male intraspecific confrontations, can be an ethologically relevant tool to investigate the neurobiology of aggressive behavior. OBJECTIVES:: To examine behavioral and neurobiological mechanisms of aggressive behavior in male Swiss mice exposed to repeated confrontations in the resident intruder paradigm. METHODS:: Behavioral analysis was performed in association with measurements of plasma corticosterone of mice repeatedly exposed to a potential rival nearby, but inaccessible (social instigation), or to 10 sessions of social instigation followed by direct aggressive encounters. Moreover, corticotropin-releasing factor (CRF) and brain-derived neurotrophic factor (BNDF) were measured in the brain of these animals. Control mice were exposed to neither social instigation nor aggressive confrontations. RESULTS:: Mice exposed to aggressive confrontations exhibited a similar pattern of species-typical aggressive and non-aggressive behaviors on the first and the last session. Moreover, in contrast to social instigation only, repeated aggressive confrontations promoted an increase in plasma corticosterone. After 10 aggressive confrontation sessions, mice presented a non-significant trend toward reducing hippocampal levels of CRF, which inversely correlated with plasma corticosterone levels. Conversely, repeated sessions of social instigation or aggressive confrontation did not alter BDNF concentrations at the prefrontal cortex and hippocampus. CONCLUSION:: Exposure to repeated episodes of aggressive encounters did not promote habituation over time. Additionally, CRF seems to be involved in physiological responses to social stressors.

Social instigation and repeated aggressive confrontations in male Swiss mice: analysis of plasma corticosterone, CRF and BDNF levels in limbic brain areas / Instigação social e confrontos agressivos repetidos em camundongos Swiss machos: análise de corticosterona plasmática e dos níveis de CRF e BDNF em áreas cerebrais límbicas

Abstract Introduction: Agonistic behaviors help to ensure survival, provide advantage in competition, and communicate social status. The resident-intruder paradigm, an animal model based on male intraspecific confrontations, can be an ethologically relevant tool to investigate the neurobiology of aggressive behavior. Objectives: To examine behavioral and neurobiological mechanisms of aggressive behavior in male Swiss mice exposed to repeated confrontations in the resident intruder paradigm. Methods: Behavioral analysis was performed in association with measurements of plasma corticosterone of mice repeatedly exposed to a potential rival nearby, but inaccessible (social instigation), or to 10 sessions of social instigation followed by direct aggressive encounters. Moreover, corticotropin-releasing factor (CRF) and brain-derived neurotrophic factor (BNDF) were measured in the brain of these animals. Control mice were exposed to neither social instigation nor aggressive confrontations. Results: Mice exposed to aggressive confrontations exhibited a similar pattern of species-typical aggressive and non-aggressive behaviors on the first and the last session. Moreover, in contrast to social instigation only, repeated aggressive confrontations promoted an increase in plasma corticosterone. After 10 aggressive confrontation sessions, mice presented a non-significant trend toward reducing hippocampal levels of CRF, which inversely correlated with plasma corticosterone levels. Conversely, repeated sessions of social instigation or aggressive confrontation did not alter BDNF concentrations at the prefrontal cortex and hippocampus. Conclusion: Exposure to repeated episodes of aggressive encounters did not promote habituation over time. Additionally, CRF seems to be involved in physiological responses to social stressors.

Resumo Introdução: Comportamentos agonísticos ajudam a garantir a sobrevivência, oferecem vantagem na competição e comunicam status social. O paradigma residente-intruso, modelo animal baseado em confrontos intraespecíficos entre machos, pode ser uma ferramenta etológica relevante para investigar a neurobiologia do comportamento agressivo. Objetivos: Analisar os mecanismos comportamentais e neurobiológicos do comportamento agressivo em camundongos Swiss machos expostos a confrontos repetidos no paradigma residente-intruso. Métodos: A análise comportamental foi realizada em associação com medidas de corticosterona plasmática em camundongos expostos repetidamente a um rival em potencial próximo, porém inacessível (instigação social), ou a 10 sessões de instigação social seguidas de encontros agressivos diretos. Além disso, o fator de liberação de corticotrofina (CRF) e o fator neurotrófico derivado do cérebro (BNDF) foram medidos no encéfalo desses animais. Camundongos controles não foram expostos à instigação social ou confrontos agressivos. Resultados: Os camundongos expostos a confrontos agressivos exibiram um padrão semelhante de comportamentos agressivos e não agressivos típicos da espécie na primeira e na última sessão. Em contraste com instigação social apenas, confrontos agressivos repetidos promoveram aumento na corticosterona plasmática. Após 10 sessões de confrontos agressivos, os camundongos apresentaram uma tendência não significativa de redução dos níveis de CRF no hipocampo, que se correlacionaram inversamente com os níveis plasmáticos de corticosterona. Por outro lado, sessões repetidas de instigação social ou confronto agressivo não alteraram as concentrações de BDNF no córtex pré-frontal e hipocampo. Conclusão: A exposição a episódios repetidos de encontros agressivos não promoveu habituação ao longo do tempo. Adicionalmente, o CRF parece estar envolvido nas respostas fisiológicas aos estressores sociais.

It is pleasant and heavy: convergence of visual contents in tobacco, alcohol and food marketing in Brazil.

The tactical use of visuoperceptual content in marketing may encourage impulsive consumption of unhealthy products. In this study, the application of visuoperceptual content was compared in advertisements used by industries of tobacco, alcohol and food. The aim was to ascertain whether similarities exist in the strategies used as variables for the selection of commercial stimuli, such as color, position and size. Scion Image and Corel Draw Graphics Suite software were used to analyze the content of a non-probabilistic sample of advertising images (N = 150). Differences were identified in the use of the colors green (p = 0.04) and red (p = 0.01), but not in the use of the color blue (p = 0.64), suggesting that induction of feelings of pleasantness resulting from the use of the color blue may be associated with the advertising in the alcohol and tobacco industries. Regarding the position of the commercial stimuli, a predominance of the use of quadrants 'C' (p = 0.00) and 'D' (p = 0.01) was found in all three industries, indicating a similar use of areas perceived as being 'heavier'. As to the size, 78% of advertisements placed the commercial stimuli within a range of 0-25% of the total image. The results showed some similarities in the use of visuoperceptual content in advertisements for tobacco, alcohol and food, especially between tobacco and alcohol. The article offers a convergence analysis of these three industries altogether, providing additional subsidies for the formulation of protection policies.

Social defeat protocol and relevant biomarkers, implications for stress response physiology, drug abuse, mood disorders and individual stress vulnerability: a systematic review of the last decade.

INTRODUCTION: Social defeat (SD) in rats, which results from male intraspecific confrontations, is ethologically relevant and useful to understand stress effects on physiology and behavior. METHODS: A systematic review of studies about biomarkers induced by the SD protocol and published from 2002 to 2013 was carried out in the electronic databases PubMed, Web of Knowledge and ScienceDirect. The search terms were: social defeat, rat, neurotrophins, neuroinflammatory markers, and transcriptional factors. RESULTS: Classical and recently discovered biomarkers were found to be relevant in stress-induced states. Findings were summarized in accordance to the length of exposure to stress: single, repeated, intermittent and continuous SD. This review found that the brain-derived neurotrophic factor (BDNF) is a distinct marker of stress adaptation. Along with glucocorticoids and catecholamines, BDNF seems to be important in understanding stress physiology. CONCLUSION: The SD model provides a relevant tool to study stress response features, development of addictive behaviors, clinic depression and anxiety, as well as individual differences in vulnerability and resilience to stress.

Heightened aggression after chronic flunitrazepam in male rats: potential links to cortical and caudate-putamen-binding sites.

RATIONALE: Higher doses of benzodiazepines induce sedation. However, in low to moderate doses, benzodiazepines can increase aggressive behavior both after acute and chronic administration. The determinants for increasing aggression after chronic intake of flunitrazepam, a so-called date rape drug, in violence-prone individuals are incompletely understood. OBJECTIVES: The aim of this study is to assess the effects of acute and chronic treatment with flunitrazepam on male aggression in resident rats. We also examined possible changes in binding to benzodiazepine receptors throughout the brain of rats that display aggressive behavior after repeated flunitrazepam treatment using quantitative receptor autoradiography. MATERIALS AND METHODS: The behaviors of the male Wistar resident rats (n = 35) toward a male intruder were recorded for 10 min twice a week. The salient aggressive and non-aggressive elements in the resident rat's behavior were analyzed. Initially, the dose-dependent effects of flunitrazepam (0.01, 0.03, 0.1, 0.18, and 0.3 mg/kg) or vehicle were determined in all rats; subsequently, 0.3 mg/kg per day flunitrazepam was administered for 42 days (n = 15), and a parallel group was treated with vehicle (n = 20). After the chronic treatment, the flunitrazepam (0, 0.01, 0.03, 0.1, 0.18, and 0.3 mg/kg) effects were again assessed. RESULTS: The most significant finding is the escalation of aggression after chronic treatment with flunitrazepam. A previously sedative 0.3 mg/kg dose of flunitrazepam engendered very high levels of attack bites, sideways threats, and aggressive postures (total aggression) after 6 weeks of daily administration. Individual differences emerged, and these were associated with decreased binding to benzodiazepine receptors, mainly in the limbic structures such as the cingulate cortex (cingulate areas 1 and 2) and caudate-putamen (posterior part) of aggressive animals, suggesting that these areas are pivotal in the control of emotional and aggressive behavior. CONCLUSIONS: Chronic flunitrazepam produces changes in receptor binding in discrete areas of the cingulate cortex and caudate-putamen that are proposed to be part of the mechanisms for increased expression of aggressive behavior.