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Features of threatening cues and the associated context influence the perceived imminence of threat and the defensive responses evoked. To provide additional knowledge about how the directionality of a threat (i.e. directed-towards or away from the viewer) might impact defensive responses in humans, participants were shown pictures of a man carrying a gun (threat) or nonlethal object (neutral) directed-away from or towards the participant. Cardiac and electrodermal responses were collected. Compared to neutral images, threatening images depicting a gun directed-towards the participant induced sustained bradycardia and an increased electrodermal response, interpreted as immobility under attack. This defensive immobility reaction is evoked by high perceived threat and inescapable situations and indicates intense action preparation. Pictures of guns directed-away from the participant induced shorter bradycardia and no significant modulation of the electrodermal response compared to neutral pictures, which might be consistent with the perception of a less threatening situation. The results show that the directionality of threat stimuli is a key factor that prompts different patterns of defensive responses.

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BACKGROUND: The flavonoid chrysin produces rapid and long-lasting anxiolytic- and antidepressant-like effects in rats. However, it is not known whether low and high doses of chrysin produce differential anti-immobility effects through the Gamma-Aminobutyric Acid sub-type A (GABAA) receptor. The goal of this work was therefore to compare low and high doses of chrysin for their effects on depression-like behavior in a longitudinal study. Moreover, chrysin was compared with the serotonergic fluoxetine and Gamma-Aminobutyric Acid (GABA)ergic allopregnanolone, and its involvement with the GABAA receptor after chronic treatment was also investigated. METHODS: Male Wistar rats were assigned to five groups (n = 8 each): vehicle, 1 mg/kg chrysin, 5 mg/kg chrysin, 1 mg/kg fluoxetine, and 1 mg/kg allopregnanolone. In the first experiment, treatments were injected daily and the effects on locomotor activity and the forced swim test were evaluated at 0, 1, 14, and 28 days of treatment, and 48 h after the final treatment. In the second experiment, similar groups were treated for 28 days with injection of 1 mg/kg picrotoxin to investigate the role of the GABAA receptor. Depending on the experimental design, one- and two-way analysis of variance (ANOVA) tests were used for statistical analysis, with p < 0.05 set as the criteria for significance. RESULTS: In both experiments, the treatments did not alter locomotor activity. However, low and high doses of chrysin, allopregnanolone, and fluoxetine gradually produced antidepressant-like effects in the forced swim test, and maintained this effect for 48 h post-treatment, except with low dose chrysin. Picrotoxin blocked the antidepressant-like effects produced by low dose chrysin, but did not affect those produced by high dose chrysin, allopregnanolone, or fluoxetine. CONCLUSIONS: The differential antidepressant-like effects caused by low and high doses of chrysin are time-dependent. Low dose chrysin produces a rapid antidepressant-like effect, whereas high dose chrysin produces a delayed but sustained the effect, even 48 h after withdrawal. The effect with high dose chrysin was similar to that observed with allopregnanolone and fluoxetine. The mechanism for the antidepressant-like effect of low chrysin appears to be GABAergic, whereas the effect of high dose chrysin may involve other neurotransmission and neuromodulation systems related to the serotonergic system.

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OBJECTIVES: The present study investigated the anti-depressive-like (anti-immobility) effect of a lectin from Moringa oleifera seeds (WSMoL) in mice. METHODS: To evaluate an acute effect, the animals were treated with WSMoL (1, 2, and 4 mg/kg, i.p.) 30 min before the tail suspension test (TST). To investigate the involvement of monoaminergic and nitrergic signaling, the mice were pre-treated with selective antagonists. The role of the WSMoL carbohydrate-recognizing domain (CRD) was verified using previous blockage with casein (0.5 mg/mL). The subacute anti-immobility effect was also evaluated by administering WSMoL (1, 2, and 4 mg/kg, i.p.) once a day for 7 d. Finally, an open field test (OFT) was performed to identify possible interferences of WSMoL on animal locomotory behavior. RESULTS: WSMoL reduced the immobility time of mice in the TST at all doses, and combined treatment with fluoxetine (5 mg/kg, i.p.) and WSMoL (1 mg/kg) was also effective. The CRD appeared to be involved in the anti-immobility effect since the solution of WSMoL (4 mg/kg) pre-incubated with casein showed no activity. The lectin effect was prevented by the pre-treatment of mice with ketanserin, yohimbine, and SCH 23390, thereby demonstrating the involvement of monoaminergic pathways. In contrast, pre-treatment with L-NAME, aminoguanidine, and L-arginine did not interfere with lectin action. WSMoL exhibited a subacute effect in the TST, thereby reducing immobility time and increasing agitation time even on the seventh day. OFT data revealed that the anti-immobility effect was not caused by interference with locomotor behavior. CONCLUSION: WSMoL elicits an anti-depressant-like effect that is dependent on monoaminergic signaling.

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RESUMO Objetivo: Neste estudo relatamos o caso de uma profissional de saúde com vivência de imobilidade tônica (IT) e posterior desenvolvimento de transtorno de estresse pós-traumático (TEPT) crônico em decorrência de trauma laboral por conta da COVID-19 que recebeu tratamento remoto com terapia cognitivo-comportamental focada no trauma (TCC-FT). Métodos: Relato de caso de uma paciente acompanhada por seis meses após o recebimento de TCC-FT remota. Resultados: Paciente do sexo feminino, de 36 anos, fisioterapeuta, que desenvolveu TEPT crônico e experienciou IT por medo da contaminação por coronavírus. As escalas psicométricas demonstraram que a TCC-FT reduziu consideravelmente os sintomas de TEPT e depressão e aumentou o apoio social e a resiliência. De acordo com o relato, o tratamento melhorou a concentração e a motivação, e reduziu o sentimento de culpa, a irritabilidade, a insegurança e o desconforto em lidar com outras pessoas. Conclusão: Este artigo demonstra que traumas decorrentes da COVID-19 podem ser capazes de desencadear IT e exemplifica um favorável desempenho da TCC-FT na melhoria global da saúde mental dos pacientes com TEPT crônico com vivência de IT.

ABSTRACT Objective: In this study, we report the case of a health professional with experience of tonic immobility (TI) and subsequent development of post-traumatic stress disorder (PTSD) as a result of occupational trauma due to COVID-19 who received remote treatment with Trauma-Focused Cognitive Behavioral Therapy (TF-CBT). Methods: A case report of a patient followed for six months after receiving remote TF-CBT. Results: A 36-year-old female patient, the physiotherapist who developed chronic PTSD and experienced TI for fear of coronavirus contamination. Psychometric scales demonstrated that TF-CBT considerably reduced PTSD and depression symptoms and increased social support and resilience. According to the report, the treatment improved concentration and motivation, and reduced feelings of guilt, irritability, insecurity, and discomfort in dealing with other people. Conclusion: This article demonstrates that trauma resulting from COVID-19 can trigger TI and exemplifies a favorable performance of TF-CBT in the global improvement of the mental health of patients with chronic PTSD who experience TI.

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ABSTRACT The COVID-19 pandemic has imposed a health crisis around the world. Health professionals are frequently exposed to stressors that put them at high risk for the development or progression of disabling mental disorders, including posttraumatic stress disorder (PTSD). To understand how pandemic stressors have affected the mental health of healthcare workers, our group conducted a longitudinal and nationwide survey. We investigated the occurrence of traumatic events related to the COVID-19 pandemic and the association between exposure to these events and PTSD symptomatology. Importantly, we also investigated factors that might increase or decrease the risk for PTSD. Depression symptoms were also investigated. The results of the first wave of the project were published in a series of three articles, each focused on different risk or protective factors. The results showed that female sex, young age, a lack of adequate personal protective equipment, social isolation and a previous history of mental illness were consistent predictors of PTSD symptoms. Healthcare workers who reported high levels of peritraumatic tonic immobility, a defensive response that is involuntary, reflexive, and evoked by an intense and inescapable threat, also exhibited an increase in the probability of being diagnosed with PTSD. On the other hand, professional recognition had a negative relationship with PTSD and depression symptoms, emerging as a significant protective factor for psychological health. The identification of protective and risk factors in these situations is crucial to guide the adoption of long-term measures in work environments that will enhance the psychological health of these professionals.

RESUMO A pandemia de COVID-19 impôs uma crise de saúde no mundo. Profissionais de saúde foram frequentemente expostos a estressores que os colocam em alto risco para o desenvolvimento ou progressão de transtornos mentais incapacitantes, incluindo o transtorno de estresse pós-traumático (TEPT). Para entender como esses estressores afetaram a saúde mental desses profissionais, nosso grupo realizou um estudo longitudinal nacional. Investigamos a ocorrência de eventos traumáticos especificamente relacionados à pandemia e a associação entre a exposição a esses eventos traumáticos e a sintomatologia do TEPT. É importante ressaltar que também investigamos fatores que podem aumentar ou diminuir o risco de TEPT. Sintomas de depressão também foram investigados. Os resultados da primeira onda do projeto foram publicados em uma série de três artigos, cada um focado em diferentes fatores de risco ou proteção. Os resultados mostraram que sexo feminino, idade jovem, falta de equipamento de proteção individual adequado, isolamento social e história prévia de doença mental foram preditores consistentes de sintomas de TEPT. Os profissionais de saúde que relataram altos níveis de imobilidade tônica, uma resposta peritraumática involuntária e reflexa evocada em situações de ameaça intensa e inescapável, exibiram aumento na probabilidade de um provável diagnóstico de TEPT. Por outro lado, reconhecimento profissional teve relação negativa com sintomas de TEPT e depressão, emergindo como importante fator de proteção para a saúde mental. Identificar fatores protetores ou de risco nessas situações é fundamental para orientar a adoção de medidas de longo prazo nos ambientes de trabalho que melhorem a saúde mental desses profissionais.

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O Transtorno de Estresse Pós-Traumático (TEPT) é uma condição debilitante que impacta significativamente a qualidade de vida dos seus portadores. Dentre vários fatores de risco para o TEPT, as reações peritraumáticas (RP), como a imobilidade tônica peritraumática (ITP), dissociação (DP) e reações físicas de pânico (RFP), estão entre as mais investigadas. No entanto, a maioria dos estudos avaliou essas RP separadamente, e o elo entre elas e o TEPT ainda não foi bem compreendido. Portanto, essa tese teve como objetivos: (i) estimar simultaneamente o efeito das três RP sobre o TEPT utilizando um instrumento validado; e (ii) avaliar se há efeito indireto da ITP sobre o TEPT mediado pelo sentimento de culpa/vergonha. Utilizamos modelagem de equações estruturais para analisar dados de 3211 participantes do Rio de Janeiro e de São Paulo. Tratamos as RP como variáveis latentes, selecionando desconfundidores específicos para cada reação. Nossas exposições foram as RP, sendo TEPT o desfecho. Calculamos odds ratios e intervalos de confiança de 95%. Utilizamos o Bayesian Information Criterion para comparar o ajuste de modelos não aninhados. Quando analisadas separadamente, todas as RP alcançaram significância estatística. No entanto, apenas DP (ORDP=1,8; IC95%:1,3-2,4) e RFP (ORRFP=2,5; IC95%:1,8-3,4) permaneceram estatisticamente significativas quando incluímos as três reações em um modelo com seus respectivos desconfundidores e correlações entre elas. Os resultados sugeriram um possível efeito da ITP sobre o TEPT (ORITP=1,4; IC95%:1,0-1,9). As interações entre as RP não foram estatisticamente significativas. Ao investigarmos o sentimento de culpa/vergonha como mediador entre ITP e TEPT, o efeito indireto alcançou apenas significância estatística limítrofe (ORITP(TNIE)=1,1; IC95%:1,0-1,2). Os efeitos direto (ORITP(PNDE)=1,3; IC95%: 0,8-1,8) e total (ORITP(TE)=1,4; IC95%:0,9-1,9) para ITP perderam significância quando todas as RP, seus desconfundidores e correlações entre elas fizeram parte do mesmo modelo. As demais RP, no entanto, permaneceram estatisticamente significativas (ORDP=1,7; IC95%:1,3-2,3 e ORRFP=2,5; IC95%:1,8-3,4). Nossos resultados mostraram que a DP e as RFP aumentaram o risco de TEPT mesmo quando consideradas em conjunto. A ITP pode ter efeito sobre o risco de TEPT, mas esse achado deve ser interpretado com cautela devido a significância limítrofe dessa RP em nosso modelo final. Também não identificamos uma mediação significativa entre ITP e TEPT pelos sentimentos de culpa/vergonha. Contudo, a significância limítrofe encontrada para o efeito indireto demanda investigações adicionais. Nossos achados reforçam a ideia de que as reações peritraumáticas devem ser analisadas e compreendidas como ocorrências simultâneas. Também seria oportuno que estudos envolvendo culpa/vergonha, ITP e TEPT focalizassem traumas caracterizados por aprisionamento e impossibilidade de escapar, dado que estas experiências são apontadas como mais susceptíveis para desencadear a ITP. (AU)

Posttraumatic stress disorder (PTSD) is a debilitating condition that greatly impacts quality of life. Among several PTSD risk factors, peritraumatic reactions (PR) such as peritraumatic tonic immobility (PTI), dissociation (PD) and physical panic reactions (PPR) are some of the most investigated. However, several studies have assessed these PR separately, and the pathway connecting them to PTSD is not well understood. Therefore, this thesis aimed to: (i) simultaneously estimate the effect of the three PR on PTSD using a validated instrument; and (ii) assess if there is an indirect effect of PTI on PTSD mediated by feelings of guilt/shame. We used structural equation modelling to analyse data from 3211 participants from Rio de Janeiro and São Paulo. We treated the PR as latent variables and selected specific confounders for each reaction. Our exposures were the PR, and PTSD was the outcome. We calculated odds ratios and 95% confidence intervals for each analysis. We also employed the Bayesian Information Criterion to compare the goodness of fit between non-nested models. Separately, all PR achieved statistically significant results. However, only PD (ORPD=1.8; 95%CI:1.3-2.4) and PPR (ORPPR=2.5; 95%CI:1.8-3.4) remained statistically significant when all three were included in a model with their respective confounders and correlations among all PR. Our findings suggested a possible effect of PTI on PTSD (ORPTI=1.4; 95%CI:1.0-1.9). Interactions between the PR were not statistically significant. When we investigated feelings of guilt/shame as the mediator between PTI and PTSD, the indirect effect achieved a borderline statistical significance (ORPTI(TNIE)=1.1; 95%CI:1.0-1.2). Direct (ORPTI(PNDE)=1.3; 95%CI:0.8-1.8) and total (ORPTI(TE)=1.4; 95%CI:0.9-1.9) effects lost their significance when all PR, their confounders and correlations were included in the same model. The other PR remained statistically significant (ORPD=1.7; 95%CI:1.3-2.3 and ORPPR=2.5; 95%CI:1.8-3.4). Our findings showed PD and PPR to increase the risk of PTSD even when considered in tandem. PTI could have an effect on PTSD, but this must be considered cautiously, as this PR only reached borderline significance in our final model. Feelings of guilt/shame did not significantly mediate PTI's effect on PTSD. However, a borderline statistical significance in the indirect effects warrants further investigation. Our findings reinforce the hypothesis that peritraumatic reactions should be analysed and understood as simultaneous occurrences, not as separate entities. It would also be appropriate for studies concerning guilt/shame, PTI and PTSD to focus on traumas characterized by imprisonment and feelings of inescapability, given that these experiences are allegedly more likely to trigger PTI. (AU)

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Introdução:No Brasil, a população considerada idosa representa a faixa etária que mais utiliza os serviçoshospitalares.Mesmo sendo um importante recurso, a admissão hospitalar frequente ou por um tempo prolongado, pode gerar comprometimentos funcionais a este público.A prática da reabilitação precoce contribui para minimizar e prevenir estesimpactos deletérios do imobilismo, favorecer a capacidade funcional, diminuindo o tempo de hospitalização, além de promover qualidade de vida. Objetivo:Observar a relevância da mobilização precoce em idosos, bem como os prejuízos acarretados pelo imobilismo durante internação hospitalar.Metodologia:Trata-se de uma revisão integrativa com busca online nas bases de dados PEDro, PUBMED, MEDLINE, LILACS e SciELO, os descritores foram: mobilização precoce, imobilismoeidosos, com seus respectivos em língua inglesa, foram selecionados artigos publicados entre os anos de 2016 a 2020, em língua portuguesa e estrangeira.Resultados:Foram selecionados cinco artigos para a discussão, sendo utilizado a deambulação precoce de precisão como limiar de segurança para reabilitação cardíaca; avaliou-se a influência da reabilitação precoce e terapia de reabilitação em pacientes com mais de 72 horas de ventilação mecânica prolongada; observou-se a intensificação da fisioterapia pós-operatória, com exercícios de respiração profunda e mobilização precoce; observou-se que a reabilitação domiciliar interdisciplinar geriátrica em idosos com fratura de quadril poderia melhorar a capacidade de locomoção e reduzir tempo de internação pós-operatória. Os achados discutidos entre os autores, apontam com unanimidade a aprovação da deambulação e mobilização precoce.Conclusões:A mobilização precoce mostrou-se eficaz tanto nos pacientes em atendimento hospitalar como no ambiente domiciliar, reduzindo significativamente os prejuízos ocasionados pelo imobilismo (AU).

Introduction:In Brazil, the population considered elderly represents the age group that most uses hospital services. Even though an important resource, frequent hospital admission orfor a prolonged period of time can generate functional impairments for this public. The practice of early rehabilitation helps to minimize and prevent the deleterious impacts of immobility, favoring functional capacity, decreasing the length of hospital stay and promoting quality of life. Objective:The study aims to observe the relevance of early mobilization in the elderly, as well as the damage caused by immobility during hospitalization. Methodology:This is an integrative review with an online search in the PEDro, PUBMED, MEDLINE, LILACS and SciELO databases. The descriptors were: early mobilization, immobility in the elderly and their respective in English. Articles published between the years 2016 to 2020, in Portuguese and foreign languages, were used. Results:Five articles were selected for discussion, using Precision Early Ambulation as a safety threshold for cardiac rehabilitation; the influence of early rehabilitation and rehabilitation therapyin patients with more than 72 hours of prolonged mechanical ventilation was evaluated; it was observed the intensification of postoperative physical therapy, with deep breathing exercises and early mobilization; geriatric interdisciplinary home rehabilitation in elderly patients with hip fractures was evaluated to improve mobility and reduce postoperative hospital stay. Discussions among the authors unanimously point to the approval of ambulation and early mobilization.Conclusions:Early mobilization proved to be effective both in patients in hospital care and in the home environment, significantly reducing the damage caused by immobility (AU).

Introducción:En Brasil, la población considerada anciana representa el grupo de edad que más utiliza los servicios hospitalarios. A pesar de que es un recurso importante, la hospitalización frecuente o por un período prolongado de tiempo puede generar deficiencias funcionales para este público. La práctica de la rehabilitación temprana ayuda a minimizar y prevenir los impactos deletéreos de la inmovilidad, favoreciendo la capacidad funcional, reduciendo el tiempo de hospitalización, además de promover la calidad de vida. Objetivo: El estudio tiene como objetivo observar la relevancia de la movilización temprana en ancianos, así como los daños causados por la inmovilización durante la hospitalización. Metodología: Esta es una revisión integradora con una búsqueda en línea de las bases de datos PEDro, PUBMED, MEDLINE, LILACS y SciELO, los descriptores fueron: movilización temprana, inmovilidad y ancianos en el idioma inglés, se seleccionaron artículos publicados entre los años de 2016 a 2020, en portugués y lenguas extranjeras. Resultados: Se seleccionaron cinco artículos para discusión, utilizando deambulación temprana de precisión como umbral de seguridad para la rehabilitación cardiaca; se evaluó la influencia de la rehabilitación temprana y la terapia de rehabilitaciónen pacientes con más de 72 horas de ventilación mecánica prolongada; hubo una intensificación de la fisioterapia posoperatoria, con ejercicios de respiración profunda y movilización precoz; Se evaluó la rehabilitación domiciliaria interdisciplinaria geriátrica en pacientes ancianos con fractura de caderapara mejorar la movilidad y reducir la estancia hospitalaria postoperatoria. Los hallazgos discutidos entre los autores apuntan unánimemente a la aprobación de la deambulación y la movilización precoz. Conclusiones: La movilización temprana demostró ser efectiva tanto en pacientes en atención hospitalaria como en el ámbito domiciliario, reduciendo significativamente el daño ocasionado por la inmovilización (AU).

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Defensive responses are neurophysiological processes crucial for survival during threatening situations. Defensive immobility is a common adaptive response, in rodents, elaborated by ventrolateral periaqueductal gray matter (vlPAG) when threat is unavoidable. It is associated with somatosensory and autonomic reactions such as alteration in the sensation of pain and rate of respiration. In this study, defensive immobility was assessed by chemical stimulation of vlPAG with different doses of NMDA (0.1, 0.3, and 0.6 nmol). After elicitation of defensive immobility, antinociceptive and respiratory response tests were also performed. Results revealed that defensive immobility was followed by a decrease in the nociceptive perception. Furthermore, the lowest dose of NMDA induced antinociceptive response without eliciting defensive immobility. During defensive immobility, respiratory responses were also disturbed. Interestingly, respiratory rate was increased and interspersed with prolonged expiratory phase of breathing. These findings suggest that vlPAG integrates three different defensive behavioral responses, contributing to the most effective defensive strategies during threatening situations.

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Menopause, natural or surgical, might facilitate the onset of psychiatric pathologies. Some reports suggest that their severity could increase if the decline of ovarian hormones occurs abruptly and before natural endocrine senescence. Therefore, we compared the effects of ovariectomy on microglia's morphological alterations, the complexity of newborn neurons, and the animal's ability to cope with stress. Young adult (3 months) and middle-aged (15 months) female Wistar rats were subjected to an ovariectomy (OVX) or were sham-operated. After 3 weeks, animals were assigned to one of the following independent groups: (1) young adult OVX + no stress; (2) young adult sham + no stress; (3) young adult OVX + stress; (4) young adult sham + stress; (5) middle-aged OVX + no stress; (6) middle-aged sham + no stress; (7) middle-aged OVX + stress; (8) middle-aged sham + stress. Acute stress was induced by forced swimming test (FST) exposure. Immobility behavior was scored during FST and 30 min after; animals were euthanized, their brains collected and prepared for immunohistochemical detection of Iba-1 to analyze morphological alterations in microglia, and doublecortin (DCX) detection to evaluate the dendrite complexity of newborn neurons. OVX increased immobility behavior, induced microglia morphological alterations, and reduced dendrite complexity of newborn neurons in young adult rats. FST further increased this effect. In middle-aged rats, the main effects were related to the aging process without OVX or stress exposure. In conclusion, surgical menopause favors in young adult rats, but not in middle-aged, the vulnerability to develop immobility behavior, retracted morphology of microglial cells, and decreased dendrite complexity of newborn neurons.

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BACKGROUND/AIMS: Anti-immobility actions of insulin in diabetic rats that are subjected to the forced swim test (FST) have been reported. In this test, low doses of antidepressants exert actions after long-term treatment, without affecting locomotor activity in healthy rats. Few studies have compared acute and chronic actions of insulin with antidepressants in healthy rats. METHODS: We hypothesized that if insulin exerts a true anti-immobility action, then its effects must be comparable to fluoxetine in both a 1-day treatment regimen and a 21-day treatment regimen in healthy, gonadally intact female Wistar rats. RESULTS: The results showed that low levels of glycemia were produced by all treatments, including fluoxetine, and glycemia was lower in proestrus-estrus than in diestrus-metestrus. None of the treatments or regimens produced actions on indicators of anxiety in the elevated plus maze. Insulin in the 1-day regimen increased the number of crossings and rearings in the open field test and caused a low cumulative immobility time in the FST. These actions disappeared in the 21-day regimen. Compared with the other treatments, fluoxetine treatment alone or combined with insulin produced a longer latency to the first period of immobility and a shorter immobility time in the chronic regimen in the FST, without affecting locomotor activity, and more pronounced actions were observed in proestrus-estrus (i.e., a true anti-immobility effect). CONCLUSION: These results indicate that insulin does not produce a true antidepressant action in healthy rats. The purported antidepressant effects that were observed were instead attributable to an increase in locomotor activity only in the 1-day regimen.

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