Activity-Dependent Synaptic Plasticity in the Medial Prefrontal Cortex of Male Rats Underlies Resilience-Related Behaviors to Social Adversity.

Individuals considered resilient can overcome adversity, achieving normal physical and psychological development, while those deemed vulnerable may not. Adversity promotes structural and functional alterations in the medial prefrontal cortex (mPFC) and hippocampus. Moreover, activity-dependent synaptic plasticity is intricately linked to neuronal shaping resulting from experiences. We hypothesize that this plasticity plays a crucial role in resilience processes. However, there is a notable absence of studies investigating this plasticity and behavioral changes following social adversity at different life stages. Consequently, we evaluated the impact of social adversity during early postnatal development (maternal separation [MS]), adulthood (social defeat [SD]), and a combined exposure (MS + SD) on behavioral outcomes (anxiety, motivation, anhedonia, and social interaction). We also examined cFos expression induced by social interaction in mPFC and hippocampus of adult male rats. Behavioral analyses revealed that SD-induced anhedonia, whereas MS + SD increased social interaction and mitigated SD-induced anhedonia. cFos evaluation showed that social interaction heightened plasticity in the prelimbic (PrL) and infralimbic (IL) cortices, dentate gyrus (DG), CA3, and CA1. Social interaction-associated plasticity was compromised in IL and PrL cortices of the MS and SD groups. Interestingly, social interaction-induced plasticity was restored in the MS + SD group. Furthermore, plasticity was impaired in DG by all social stressors, and in CA3 was impaired by SD. Our findings suggest in male rats (i) two adverse social experiences during development foster resilience; (ii) activity-dependent plasticity in the mPFC is a foundation for resilience to social adversity; (iii) plasticity in DG is highly susceptible to social adversity.

The rostral ventromedial medulla modulates pain and depression-related behaviors caused by social stress.

ABSTRACT: The rostral ventromedial medulla (RVM) is a crucial structure in the descending pain modulatory system, playing a key role as a relay for both the facilitation and inhibition of pain. The chronic social defeat stress (CSDS) model has been widely used to study stress-induced behavioral impairments associated with depression in rodents. Several studies suggest that CSDS also causes changes related to chronic pain. In this study, we aimed to investigate the involvement of the RVM in CSDS-induced behavioral impairments, including those associated with chronic pain. We used chemogenetics to activate or inhibit the RVM during stress. The results indicated that the RVM is a vital hub influencing stress outcomes. Rostral ventromedial medulla activation during CSDS ameliorates all the stress outcomes, including social avoidance, allodynia, hyperalgesia, anhedonia, and behavioral despair. In addition, RVM inhibition in animals exposed to a subthreshold social defeat stress protocol induces a susceptible phenotype, facilitating all stress outcomes. Finally, chronic RVM inhibition-without any social stress stimulus-induces chronic pain but not depressive-like behaviors. Our findings provide insights into the comorbidity between chronic pain and depression by indicating the involvement of the RVM in establishing social stress-induced behavioral responses associated with both chronic pain and depression.

Distinct roles of the left and right prelimbic cortices in the modulation of ethanol consumption in male mice under acute and chronic social defeat stress.

RATIONALE: Chronic stress exposure disrupts the medial prefrontal cortex's (mPFC) ability to regulate impulses, leading to the loss of control over alcohol drinking in rodents, emphasizing the critical role of this forebrain area in regulating alcohol consumption. Moreover, chronic stress exposure causes lateralization of mPFC functions with volumetric and functional changes, resulting in hyperactivity in the right hemisphere and functional decrease in the left. OBJECTIVES: This study investigated the inhibitory role of the left prelimbic cortex (LPrL) on ethanol consumption induced by chronic social defeat stress (SDS) in male mice and to examine if inactivation of the LPrL causes disinhibition of the right mPFC, leading to an increase in ethanol consumption. We also investigated the role of lateralization and neurochemical alterations in the mPFC related to ethanol consumption induced by chronic SDS. To this end, we examined the activation patterns of ΔFosB, VGLUT2, and GAD67 in the left and right mPFC. RESULTS: Temporarily blocking the LPrL or right PrL (RPrL) cortices during acute SDS did not affect male mice's voluntary ethanol consumption in male mice. When each cortex was blocked in mice previously exposed to chronic SDS, ethanol consumption also remained unaffected. However, male mice with LPrL lesions during chronic SDS showed an increase in voluntary ethanol consumption, which was associated with enhanced ΔFosB/VGLUT2-positive neurons within the RPrL cortex. CONCLUSIONS: The results suggest that the LPrL may play a role in inhibiting ethanol consumption induced by chronic SDS, while the RPrL may be involved in the disinhibition of ethanol consumption.

A culpa é de junho de 2013? Os caminhos da alienação política e a ascensão da extrema direita no Brasil / Is June 2013 to blame? The paths of political alienation and the rise of the far right in Brazil / Juin 2013 est-il coupable ? Les chemins de l'aliénation politique et la montée de l'extrême droite au Brésil / ¿Es junio de 2013 el culpable? Los caminos de la alienación política y el ascenso de la extrema derecha en Brasil

Este artigo apresenta as principais causas e o significado das manifestações maciças de junho de 2013 para discutir como a derrota de seu impulso contribuiu para que uma extrema direita formada posteriormente viesse a se apropriar do sentimento de insatisfação com o sistema político, manipulando-o em um sentido regressivo. Como suporte à sua reflexão, o autor recorre às categorias teóricas de alienação política e angústia social em Franz Neumann

This paper discusses the main causes of and meanings attributed to the mass demonstrations of June 2013 in Brazil, arguing that the defeat of the movement's momentum contributed to the later appropriation and regressive manipulation of the political dissatisfaction by the far right. Franz Neumann's theoretical categories of political alienation and social anxiety help to support the reflection

Cet article porte sur les principales causes et les sens apportées aux manifestations massifs du mois juin de 2013 au Brésil, en affirmant que la défaite de leur dynamisme a contribué pour qu'une extrême droite leur ait confisqué le sentiment d'insatisfaction à l'égard du système politique, en le manipulant dans un sens régressif. Pour soutenir sa réflexion, l'auteur recourt aux concepts d'aliénation politique et d'angoisse sociale chez Franz Neumann

Este artículo presenta las principales causas y el significado de las manifestaciones masivas de junio de 2013 en Brasil para discutir cómo la derrota de su impulso contribuyó para que una extrema derecha, que posteriormente se formará, se apropiara del sentimiento de descontento con el sistema político brasileño, manipulándolo en sentido regresivo. Se utiliza como aporte las categorías teóricas de alienación política y angustia social de Franz Neumann

Role of the rostral dorsomedial column of the periaqueductal gray during social defeat in rats.

Previous studies showed that the dorsal premammillary nucleus of the hypothalamus (PMD) is involved in social passive defensive behaviors likely to be meditated by descending projections to the periaqueductal gray (PAG). We focused on the rostral dorsomedial PAG (rPAGdm) to reveal its putative neural mechanisms involved in mediating social defensive responses. By combining retrograde tracing and FOS expression analysis, we showed that in addition to the PMD, the rPAGdm is influenced by several brain sites active during social defeat. Next, we found that cytotoxic lesions of the rPAGdm drastically reduced passive defense and did not affect active defensive responses. We then examined the rPAGdm's projection pattern and found that the PAGdm projections are mostly restricted to midbrain sites, including the precommissural nucleus, different columns of the PAG, and the cuneiform nucleus (CUN). Also, we found decreased FOS expression in the caudal PAGdm, CUN, and PMD after the rPAGdm was lesioned. The results support that the rPAGdm mediates passive social defensive responses through ascending paths to prosencephalic circuits likely mediated by the CUN. This study provides further support for the role of the PAG in the modulation of behavioral responses by working as a unique hub for influencing prosencephalic sites during the mediation of aversive responses.

Behavioral flexibility impacts on coping and emotional responses in male mice submitted to social defeat stress.

Behavioral flexibility permits the appropriate behavioral adjustments in response to changing environmental demands. The present study aimed to evaluate if variability in baseline flexibility can enable differences in coping strategies, changes in neuroplasticity, and behavioral outcomes in responses to chronic social defeat stress (CSDS). Male C57BL6 mice were submitted to the Morris Water Maze (MWM) using an extended protocol for reversal learning to assess. The animals were divided into low and high behavioral flexibility groups based on their performance on the last day of acquisition versus the four days of reversal learning. The CSDS was applied for ten consecutive days, and coping strategies were evaluated during the physical interaction on the first and last day of stress. A battery of behavioral tests to assess social and emotional behavior was conducted 24 h after the CSDS protocol. The complexity of prefrontal cortex (PFC) neuronal morphology was evaluated by the Golgi-Cox method. Animals with High Flexibility exhibited changes in their CSDS coping strategies, from active to passive coping, during the CSDS protocol. Low Flexibility mice had no alterations in the coping strategies during CSDS. After social stress, High Flexibility was associated with reduced social interaction with an aggressive Swiss mouse, higher latency to immobility in the tail suspension test, and reduced latency to self-care in the sucrose splash test. High Flexibility mice also displayed higher dendritic complexity on pyramidal neurons from the prelimbic and infralimbic prefrontal cortex compared to Low Flexibility mice. These results suggest That High Flexibility is associated with increased neuroplasticity in cortical areas and better emotional responses related to behavioral despair and motivation. However, exposure to CSDS reversed the beneficial effects of High Flexibility in male mice. Thus, this study suggests that baseline variability in behavioral flexibility, even in inbred strains, might be associated with differences in coping strategies, PFC morphology, and behavioral responses to social stress.

(In)tolerância como política: os discursos de direita e de esquerda no facebook / (In)tolerance as policy: the rightist and leftist discourses on facebook / (In)tolerancia como política: los discursos de la derecha y la izquierda en facebook

Este estudo tem como objetivo analisar traços da mentalidade potencialmente autoritária a partir do discurso de usuários do Facebook vinculados a páginas de cunho político autodeclarado de direita e de esquerda no Brasil. A Netnografia é utilizada como aporte metodológico para imersão on-line nas páginas "Eu era Direita e não sabia" e "Jovens de Esquerda", selecionadas por meio do Facebook Audience Insights, ferramenta disponibilizada pelo Facebook. Delas, foram extraídas oito postagens com maior engajamento (número de comentários, curtidas e compartilhamentos), identificadas pelo Netvizz. Foram coletados 3.489 comentários, os quais foram organizados em um corpus textual submetido ao software IRAMUTEQ e analisados sob a perspectiva da análise crítica imanente da teoria crítica. Como resultado, apresenta-se a forma como o pensamento autoritário se manifesta na racionalização da sociedade contemporânea e nas práticas discursivas em redes sociais on-line, enraizada no âmbito sociopolítico brasileiro, ameaçando o processo democrático e a construção de uma sociedade plural e liberta.(AU)

This study aims to analyze traits of the potentially authoritarian mentality from the speech of Facebook users linked to political pages self-declared as rightist and leftist in Brazil. Netnography is used as a methodological contribution for online immersion in the pages "Eu era Direita e não sabia" and "Jovens de Esquerda" selected via Facebook Audience Insights, a tool provided by Facebook. From these, eight posts with greater engagement (number of comments, likes and shares), identified by Netvizz, were extracted. We collected 3,489 comments, which were organized in a textual corpus submitted to IRAMUTEQ software and analyzed from the perspective of immanent critical analysis of Critical Theory. As a result, we present the way in which authoritarian thinking manifests itself in the rationalization of contemporary society and in discursive practices in online social networks, rooted in the Brazilian socio-political sphere, threatening the democratic process and the construction of a plural and free society.(AU)

Este estudio tiene como objetivo analizar las huellas de la mentalidad potencialmente autoritaria a partir de los discursos de usuarios en Facebook vinculados a páginas políticas autodeclaradas de derecha y de izquierda en Brasil. La netnografía se utiliza como marco metodológico para la inmersión en línea en las páginas "Eu era Direita e não sabia" y "Jovens de Esquerda", seleccionadas por Facebook Audience Insights, herramienta proporcionada por Facebook. Se extrajeron las ocho publicaciones con mayor compromiso (número de comentarios, gustos y compartidas), identificadas por Netvizz. Se recogieron 3.489 comentarios, los cuales fueron organizados en un corpus textual sometido al software IRAMUTEQ y analizado bajo la perspectiva del análisis crítico inmanente de la teoría crítica. Los resultados presentan la forma en que el pensamiento autoritario se manifiesta en la racionalización de la sociedad contemporánea y en prácticas discursivas en redes sociales en línea, arraigada en el ámbito sociopolítico brasileño, que amenazan el proceso democrático y la construcción de una sociedad plural y liberada.(AU)

(Sobre)viver na rua: narrativas das pessoas em situação de rua sobre a rede de apoio / (About) living on the street: narratives of homeless people about the support network / (Sobre)vivir en la calle: narrativas de personas en situación de calle sobre la red de apoyo

A população em situação de rua (PSR), em seu cotidiano, se relaciona com diferentes pessoas, grupos e/ou coletivos ligados à execução das políticas públicas, às organizações não governamentais, familiares ou a membros da sociedade civil. Pensar nessas dinâmicas de trabalho, cooperação e auxílio remete a pensar sobre uma rede de apoio que constrói estratégias com essa população. Tendo presente essas problematizações, este estudo teve como objetivo analisar as narrativas das pessoas em situação de rua sobre como é produzida sua rede de apoio. Para tanto, foi realizado um estudo qualitativo, de orientação etnográfica, sendo utilizada a observação participante, registros em diário de campo e entrevistas narrativas. Participaram seis pessoas em situação de rua que recebem alimentação ofertada por projetos sociais em uma cidade do interior do Rio Grande do Sul. Os dados produzidos foram analisados a partir da Análise Temática. As análises expressam as especificidades das narrativas das trajetórias de vida associadas à chegada às ruas e à composição de uma rede de apoio na rua. Ao conhecer como se produz e opera essa rede de apoio, a partir das narrativas das pessoas em situação de rua, problematiza-se a complexidade dessa engrenagem e o desafio de produzir ações integradas entre as diferentes instâncias da rede. Nisso, destaca-se a potencialidade de práticas que levem conta à escuta, ao diálogo e à articulação na operacionalização de políticas públicas atentas às necessidades dessa população.(AU)

The street population, in their daily lives, relates to different people, groups and/or collectives linked to the execution of public policies, to non-governmental organizations, family members, or to members of civil society. Thinking about these dynamics of work, cooperation, and assistance leads to thinking about a support network that builds strategies with this population. Having these problematizations in mind, this study aims to analyze the narratives of homeless people about how their support network is produced. To this end, a qualitative study was carried out, with ethnographic orientation, using participant observation, records in a field diary, and narrative interviews. Participated in the research six homeless people who receive food offered by social projects in a municipality in the interior of Rio Grande do Sul. The data produced were analyzed using the Thematic Analysis. The analyzes express the specifities of the narratives of life trajectories associated with the arrival on the streets and the composition of a support network on the street. By knowing how the support network is produced and operated, the complexity of this gear and the challenge of producing integrated actions between the different instances of the network are problematized. Thus, it highlights the potential of practices that consider listening, dialogue, and articulation in the operationalization of public policies that are attentive to the needs of this population.(AU)

Las personas en situación de calle en su cotidiano se relacionan con distintas personas, grupos y/o colectivos, que están vinculados a la ejecución de políticas públicas, organizaciones no gubernamentales, familiares o miembros de la sociedad civil. Pensar en estas dinámicas de trabajo, cooperación y ayuda nos lleva a una red de apoyo que construye estrategias con estas personas. Teniendo en cuenta esta problemática, este estudio tiene como objetivo analizar las narrativas de las personas en situación de calle acerca de cómo se produce su red de apoyo. Con este fin, se realizó un estudio cualitativo, etnográfico, utilizando observación participante, registros de diario de campo y entrevistas narrativas. Este estudio incluyó a seis personas en situación de calle que reciben alimentos ofrecidos por proyectos sociales en una ciudad del interior de Rio Grande do Sul (Brasil). Se utilizó el Análisis Temático. Los análisis expresan las especificidades de las narrativas de las trayectorias de vida asociadas con la llegada a las calles y la composición de una red de apoyo en la calle. Al saber cómo se produce y opera la red de apoyo, a partir de las narrativas de las personas en la calle, se problematizan la complejidad de este equipo y el desafío de producir acciones integradas entre las diferentes instancias de la red. Destaca el potencial de las prácticas que tienen en cuenta la escucha, el diálogo y la articulación en la implementación de políticas públicas que estén atentas a las necesidades de esta población.(AU)

A disciplina psicologia do esporte nos cursos de psicologia e educação física / Sports psychology in psychology and physical education courses / La materia psicología del deporte en los cursos de psicología y educación física

Este discute a representatividade da disciplina Psicologia do Esporte nos cursos de Psicologia e Educação Física em instituições de ensino superior reconhecidas pelo MEC e situadas na região Sul do país. Foi realizado um estudo documental, com base nos currículos das Instituições. Os resultados revelaram que no Sul do Brasil 21,02% dos cursos de Psicologia, 41,96% dos cursos de bacharelado em Educação Física e apenas 14,83% dos cursos de licenciatura em Educação Física apresentam a disciplina Psicologia do Esporte em sua grade curricular. Observou-se que a disciplina é ofertada mais frequentemente em regime obrigatório nos cursos de bacharelado em Educação Física. Nos cursos de Psicologia, quando ofertada, costuma ser optativa. Os resultados evidenciam uma maior oferta da disciplina para os estudantes de Educação Física, em relação aos de Psicologia, o que pode estar relacionado ao próprio contexto de surgimento da disciplina e sua popularização no meio acadêmico. Para que esse panorama possa mudar e se possa oferecer uma formação adequada no curso de Psicologia para fomentar essa opção de carreira, há necessidade de se repensar o currículo e o próprio perfil do egresso, de forma a dar mais oportunidade aos estudantes para que conheçam as bases teóricas e os campos de aplicação da Psicologia do Esporte. Tal lacuna pode acarretar a fragilização da disseminação desse conhecimento aos estudantes de graduação e a consequente ocupação do mercado de trabalho.(AU)

This study discusses the representativeness of Sports Psychology in Psychology and Physical Education courses at higher education institutions from Southern Brazil. A documentary study was conducted based on the institutions' curricula. Results show that 21.02% of the Psychology major, 41.96% of the bachelor's in Physical Education, and only 14.83% of the license in Physical Education offer Sports Psychology in their curricula. Sports Psychology is most often offered as a compulsory subject in the bachelor's program in Physical Education, whereas Psychology courses offer it mainly as an elective. Physical Education students have greater contact with the discipline when compared with Psychology students, which may be explained by its context of development and popularization in the academic environment. To change this scenario and offer adequate education in the Psychology programs to foster this career option, institutions must rethink their curriculum and the graduate profile itself. This would give students better opportunity to get to know its theoretical bases and fields of application. Such a gap can hinder the dissemination of this knowledge to undergraduate students and the consequent labor market occupation.(AU)

El objetivo de este estudio es discutir la representatividad de la materia Psicología del Deporte en los cursos de Psicología y Educación Física en instituciones de educación superior de la región Sur de Brasil, reconocidas por el Ministerio de Educación (MEC). Se realizó un estudio documental, basado en los planes de estudio de las instituciones. Los resultados revelaron que, en el Sur de Brasil, el 21,02% de los cursos de Psicología, el 41,96% de los cursos de licenciatura en Educación Física y sólo el 14,83% de los cursos de profesorado en Educación tienen la materia Psicología del Deporte en sus planes de estudio. Se observó que la materia Psicología del Deporte se ofrece con mayor frecuencia como asignatura obligatoria en los cursos de licenciatura en Educación Física. Cuando se ofrece en los cursos de Psicología, es una materia optativa. Los resultados muestran una mayor oferta para los estudiantes de Educación Física en comparación con Psicología, lo que puede estar relacionado con el contexto del surgimiento de la Psicología del Deporte como materia y su popularización en el ámbito académico. Para que este escenario cambie y sea posible ofrecer una formación adecuada en el curso de Psicología con el fin de fomentar esta opción de carrera, es necesario repensar el plan de estudios y el perfil del egresado, así los estudiantes tendrán más oportunidades de conocer sus bases teóricas y sus campos de actuación. Tal brecha puede debilitar la difusión de este conocimiento a los estudiantes de grado y la consecuente ocupación en el mercado laboral.(AU)

Long-term effects of stress resilience: Hippocampal neuroinflammation and behavioral approach in male rats.

Resilience to stress is the ability to quickly adapt to adversity. There is evidence that exposure to prolonged stress triggers neuroinflammation what produces individual differences in stress vulnerability. However, the relationship between stress resilience, neuroinflammation, and depressive-like behaviors remains unknown. The aim of this study was to analyze the long-term effects of social defeat stress (SDS) on neuroinflammation in the hippocampus and depressive-like behaviors. Male rats were subjected to the SDS paradigm. Social interaction was analyzed 1 and 2 weeks after ending the SDS to determine which animals were susceptible or resilient to stress. Neuroinflammation markers glial fibrillary acidic protein, ionized calcium-binding adaptor molecule 1, and elevated membrane permeability in astrocytes and microglia, as well as depressive-like behaviors in the sucrose preference test and forced swim test were evaluated in all rats. One week after SDS, resilient rats increased their sucrose preference, and time spent in the floating behavior decreased in the forced swim test compared to susceptible rats. Surprisingly, resilient rats became susceptible to stress, and presented neuroinflammation 2 weeks after SDS. These findings suggest that SDS-induced hippocampal neuroinflammation persists in post-stress stages, regardless of whether rats were initially resilient or not. Our study opens a new approach to understanding the neurobiology of stress resilience.

Social defeat stress-induced hyperalgesia is mediated by nav 1.8+ nociceptive fibers.

Recently the voltage-gated sodium (Nav) channels began to be studied as possible targets for analgesic drugs. In addition, specific Nav 1.8 blockers are currently being used to treat some types of chronic pain pathologies such as neuropathies and fibromyalgia. Nav 1.8+ fibers convey nociceptive information to brain structures belonging to the limbic system, which is involved in the pathophysiology of major depressive disorders. From this, using a model of chronic social defeat stress (SDS) and intrathecal injections of Nav 1.8 antisense, this study investigated the possible involvement of Nav 1.8+ nociceptive fibers in SDS- induced hyperalgesia in C57/BL mice. Our results showed that SDS induced a depressive-like behavior of social avoidance and increased the sensitivity to mechanical (electronic von Frey test) and chemical (capsaicin test) nociceptive stimuli. We also showed that intrathecal injection of Nav 1.8 antisense reversed the SDS-induced hyperalgesia as demonstrated by both, mechanical and chemical nociceptive tests. We confirmed the antisense efficacy and specificity in a separate no-defeated cohort through real-time PCR, which showed a significant reduction of Nav 1.8 mRNA and no reduction of Nav 1.7 and Nav 1.9 in the L4, L5 and L6 dorsal root ganglia (DRG). The present study advances the understanding of SDS-induced hyperalgesia, which seems to be dependent on Nav 1.8+ nociceptive fibers.

Anxiogenesis induced by social defeat in male mice: Role of nitric oxide, NMDA, and CRF1 receptors in the medial prefrontal cortex and BNST.

Nitric oxide (NO) release in the right medial prefrontal cortex (RmPFC) produces anxiogenesis. In the bed nucleus of the stria terminalis (BNST), a region that receives neuronal projections from the mPFC, NO provokes anxiety, an effect that is blocked by local injections of corticotrophin-releasing factor type 1 receptor (CRF1) or n-methyl-d-aspartate receptor (NMDAr) antagonist. Anxiety is also enhanced by social defeat stress, and chronic stress impairs and facilitates, respectively, PFC and BNST roles in modulating behavioral responses to aversive situations. This study investigated whether the (i) chronic social defeat stress (CSDS) increases NO signaling in the mPFC; and/or (ii) anxiogenic effects provoked by the intra-RmPFC injection of NOC-9 (an NO donor) or by CSDS are prevented by intra-BNST injections of AP-7 (0.05 nmol) or CP 376395 (3.0 nmol), respectively, NMDAr and CRF1 antagonists, in male Swiss-Webster mice exposed to the elevated plus-maze (EPM). Results showed that (a) CSDS increased anxiety (i.e., reduced open-arm exploration) and repeatedly activated nNOS-containing neurons, as measured by ΔFosB (a stable nonspecific marker of neural activity) + nNOS double-labeling, in the right (but not left) mPFC, (b) NOC-9 in the RmPFC also increased anxiety, and (c) both CSDS and NOC-9 effects were reversed by injections of AP-7 or CP 376395 into the BNST. These results suggest that NMDA and CRF1 receptors located in BNST play an important role in the modulation of anxiety provoked by NO in the RmPFC, as well as by chronic social defeat in mice.

Therapeutic and Preventive Effect of Voluntary Running Wheel Exercise on Social Defeat Stress (SDS)-induced Depressive-like Behavior and Chronic Pain in Mice.

Major depressive disorders (MDD) and chronic pain (CP) affect significant portion of the world's population and have high comorbidity rate. Social defeat stress (SDS) model was standardized in mice and can trigger depressive-like behavior and chronic pain. Based especially on clinical trials showing an effective preventive and therapeutic effect of physical exercise on CP and symptoms associated with MDD, this study aimed to investigate if the voluntary running wheel exercise can exert these effects in mice submitted to the 10-day SDS protocol, using fluoxetine as positive control. For this, we ran two set of experiments: in the first set mice started performing voluntary running wheel exercise after submitted to SDS and, in the second set, mice performed voluntary running wheel exercise before and during SDS. Mechanical and chemical hyperalgesia was analyzed through electronic von Frey and capsaicin test, respectively. Depressive-like behavior was assessed through social interaction test. Our results showed that the voluntary running wheel exercise was more effective than fluoxetine reversing the SDS-induced persistent hyperalgesia and both, fluoxetine and voluntary running wheel exercise, was effective reversing SDS-induced social avoidance. Also, voluntary running wheel exercise is an effective tool preventing both hyperalgesia and social avoidance induced by SDS. To the best of our knowledge, this was the first study using physical exercise as a therapeutic and preventive tool for chronic pain and depressive-like behavior simultaneously induced by social stress.

Inhibition of the left medial prefrontal cortex (mPFC) prolongs the social defeat-induced anxiogenesis in mice: Attenuation by NMDA receptor blockade in the right mPFC.

Chemical inhibition and nitrergic stimulation of the left and right medial prefrontal cortex (L and RmPFC), respectively, provoke anxiety in mice. Moreover, LmPFC inhibition immediately followed by a single social defeat stress (SDS) led to anxiogenesis in mice exposed to the elevated plus maze (EPM) 24 h later. Given that glutamate NMDA (N-methyl-D-aspartate) receptors are densely present in the mPFC, we investigated (i) the time course of LmPFC inhibition + SDS-induced anxiogenesis and (ii) the effects of intra-RmPFC injection of AP-7 (a NMDA receptor antagonist) on this long-lasting anxiety. Male Swiss mice received intra-LmPFC injection of CoCl2 (1 mM) and 10 min later were subjected to a single SDS episode and then (i) exposed to the EPM 2, 5, or 10 days later or (ii) 2 days later, received intra-RmPFC injection of AP-7 (0.05 nmol) and were exposed to the EPM to observe the percentage of open arm entries and time (%OE; %OT) and frequency of closed arm entries (CE). Dorsal but not ventral LmPFC inhibition + SDS reduced open arm exploration 2, 5, and 10 days later relative to that of saline-treated or non-defeated mice. Moreover, this effect is not due to locomotor impairment as assessed using the general activity. Intra-RmPFC AP-7 injection 2 days after LmPFC inhibition + SDS prevented this type of anxiogenesis. These results suggest that the integrity of the LmPFC is important for mice to properly cope with SDS, and that NMDA receptor blockade in the RmPFC facilitates resilience to SDS-induced anxiogenesis in mice.