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 influence of paraventricular nucleus of the hypothalamus soluble guanylate cyclase on autonomic and neuroendocrine responses to acute restraint stress in rats.

The paraventricular nucleus of the hypothalamus (PVN) regulates physiological and behavioural responses evoked by stressful stimuli, but the local neurochemical and signalling mechanisms involved are not completely understood. The soluble guanylate cyclase (sGC) within the PVN is implicated in autonomic and cardiovascular control in rodents under resting conditions. However, the involvement of PVN sGC-mediated signalling in stress responses is unknown. Therefore, we investigated the role of sGC within the PVN in cardiovascular, autonomic, neuroendocrine, and local neuronal responses to acute restraint stress in rats. Bilateral microinjection of the selective sGC inhibitor ODQ (1 nmol/100 nl) into the PVN reduced both the increased arterial pressure and the drop in cutaneous tail temperature evoked by restraint stress, while the tachycardia was enhanced. Intra-PVN injection of ODQ did not alter the number of Fos-immunoreactive neurons in either the dorsal cap parvocellular (PaDC), ventromedial (PaV), medial parvocellular (PaMP), or lateral magnocelllular (PaLM) portions of the PVN following acute restraint stress. Local microinjection of ODQ into the PVN did not affect the restraint-induced increases in plasma corticosterone concentration. Taken together, these findings suggest that sGC-mediated signalling in the PVN plays a key role in acute stress-induced pressor responses and sympathetically mediated cutaneous vasoconstriction, whereas the tachycardiac response is inhibited. Absence of an effect of ODQ on corticosterone and PVN neuronal activation in and the PaV and PaMP suggests that PVN sGC is not involved in restraint-evoked hypothalamus-pituitary-adrenal (HPA) axis activation and further indicates that autonomic and neuroendocrine responses are dissociable at the level of the PVN.

Pubertal stress in male rats: Effects on juvenile play behavior and adult sexual partner preference.

Puberty is a period of brain organization impacting the expression of social and sexual behaviors. Here, we assessed the effects of an acute pubertal stressor (immune challenge) on the expression of juvenile play (short-term) and sexual partner preference (long-term) in male rats. Juvenile play was assessed over ten trials at postnatal days (PND) (31-40) with age- and sex-matched conspecifics, and at PND35 males received a single injection of lipopolysaccharide (LPS, 1.5 mg/kg i.p.) or saline. Then, sexual partner preference was assessed at PND 60, 64, and 68, in a three-compartment chamber with a sexually receptive female and a male as potential partners simultaneously. The results confirmed that a single injection of LPS during puberty induced sickness signs indicative of an immune challenge. However, juvenile play was not affected by LPS treatment during the following days (PND36-40), nor was sexual behavior and partner preference for females in adulthood. These findings highlight that, while other studies have shown that LPS-induced immunological stress during puberty affects behavior and neuroendocrine responses, it does not affect juvenile play and sexual behavior in male rats. This suggests a remarkable resilience of these behavioral systems for adaptation to stressful experiences mediated by immune challenges during critical periods of development. These behaviors, however, might be affected by other types of stress.

Cumulative lifetime stressor exposure impairs stimulus-response but not contextual learning.

Greater exposure to stressors over the life course is believed to promote striatum-dependent over hippocampus-dependent learning and memory processes under stressful conditions. However, little research in this context has actually assessed lifetime stressor exposure and, moreover, it remains unknown whether greater cumulative lifetime stressor exposure exerts comparable effects on striatum-dependent learning and hippocampus-dependent learning in non-stressful contexts. To investigate this issue, we used the Stress and Adversity Inventory for Adults (Adult STRAIN) and Multicued Search Task to investigate the relation between cumulative lifetime stressor exposure and striatum-dependent stimulus-response learning and hippocampus-dependent contextual learning under non-stressful conditions among healthcare professionals (N = 205; 157 females, 48 males; Age: M = 34.23, SD 9.3, range 20-59 years). Individuals with moderate, but not low, cumulative lifetime stressor exposure exhibited impaired learning for stimulus-response associations. In contrast, learning for context associations was unrelated to participants' lifetime stressor exposure profiles. These results thus provide first evidence that cumulative lifetime stressor exposure may have negative consequences on human striatum-dependent stimulus-response learning under non-stressful environmental conditions.

Identifying physiological indicators of the cognitive, thermal, and combined (cognitive-thermal) stress conditions.

Physiologically based stress detection systems have proven to be effective in identifying different stress conditions in the body to determine the source of stress and be able to counteract it. However, some stress conditions have not been widely studied, including thermal stress, cognitive stress, and combined (thermal-cognitive) stress conditions, which are frequently encountered in work or school environments. In order to develop systems to detect and differentiate these conditions, it is necessary to identify the physiological indicators that characterize each of them. The present research aims to identify which physiological indicators (heart rate, respiratory rate, galvanic skin response, and local temperature) could differentiate different stress conditions (no-stress, cognitive stress, thermal stress, and combined (thermal-cognitive) stress conditions). Thirty participants were exposed to cognitive, thermal, and combined stress sources while recording their physiological signals. The findings indicate that both mean heart rate and mean galvanic skin response identify moderate thermal and cognitive stress conditions as distinct from a no-stress condition, yet they do not differentiate between the two stress conditions. Additionally, heart rate uniquely identifies the cognitive-thermal stress condition, effectively distinguishing this combined stress condition from the singular stress conditions and the no-stress condition. Mean local temperature specifically signals thermal stress conditions, whereas mean respiratory rate accurately identifies cognitive stress conditions, with both indicators effectively separating these conditions from each other and from the no-stress condition. This is the first basis for differentiating thermal and cognitive stress conditions through physiological indicators.

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.

Stress and fear responses of slow-growing broiler chickens to light stimulation initiated at different phases of embryonic development

Photo-incubation can influence the fear and stress responses of poultry. However, it is unclear how photostimulation initiated at different phases of development influences the welfare status of slow-growing broiler birds. 500 Sasso eggs were assigned to 4 treatments; some were incubated in the dark throughout incubation (TA), while TB, TC and TD were photo-stimulated (12L:12D) from days 1, 7, and 14 of incubation, respectively, until hatch using a 6,500k LED at 788 clux intensity. Birds were raised in 5 replicates per treatment with 16 birds per replicate using a 6,500k LED (at 28 clux) and a photoperiod of 16L:8D. Fear (emergence, tonic immobility, isolation and inversion tests) and stress response (physical asymmetry) of 10 birds per treatment were examined. At the end of the three-week brooding, all parameters measured were not significantly influenced (P > 0.05) by the onset of photo-incubation. At slaughter age (12 weeks), physical asymmetry was significantly higher (P < 0.05) in TA compared to the other treatments. The frequency of isolation vocalisation was significantly lower (P < 0.05) in TB compared to TA, and latency to rightness during tonic immobility was significantly higher (P < 0.05) in TA compared to the other treatments. Latency to emerge was significantly longer (P < 0.05) in TA compared to TC and TD. The frequency of wing flaps during inversion was significantly higher (P < 0.05) in TA and TD. Conclusively, photo-incubating eggs reduce stress and fear, and initiating photo-incubation during the first phase of incubation is more beneficial.

Psychophysiological Stress Markers During Preseason Among Elite Female Soccer Players.

ABSTRACT: Botelho, R, Abad, CCC, Spadari, RC, Winckler, C, Garcia, MC, and Guerra, RLF. Psychophysiological stress markers during preseason among elite female soccer players. J Strength Cond Res 36(6): 1648-1654, 2022-This study aimed to investigate changes and correlations between mood states and various physiological stress markers after a 7-week preseason period among elite female soccer players. Twenty-four elite female soccer players participated in this study (26.4 ± 3.7 years). Their internal training load, mood states, day and evening salivary testosterone and cortisol concentrations, blood creatine kinase concentration (CK), and heart rate variability (HRV) were assessed during the first week of preseason (PRE), and again 7 weeks after a systematic training period (END). After the preseason, there were significant increases in subject negative mood scales (p ≤ 0.03; Effect Size [ES] > 0.60), total mood scores (p = 0.01; QI = 100/0/0; ES = 1.32), day and evening testosterone and cortisol concentrations (p ≤ 0.03; ES > 0.54), and CK concentrations (p = 0.01; QI = 100/0/0; ES = 1.54). Correlations were found between cortisol and tension (r = 0.53 and 0.60; p ≤ 0.02), cortisol and confusion (r = 0.75; p = 0.01), and cortisol and the LF/HF index of HRV (r = -0.52; p = 0.04). Mood states (except vigor), salivary testosterone, and cortisol concentrations, as well as CK, showed significant changes after a 7-week systematic training system. The cortisol was the factor most highly related to various mood states (including tension and confusion), and with the HRV indices. Coaches and researchers can use these data to design, monitor, and control soccer training programs, in particular throughout the preseason period.

Differential roles of prelimbic and infralimbic cholinergic neurotransmissions in control of cardiovascular responses to restraint stress in rats.

Previous studies showed a prominent role of the medial prefrontal cortex (mPFC), especially the prelimbic (PL) and infralimbic (IL) subregions, in behavioral and physiological responses to stressful stimuli. Nevertheless, the local neurochemical mechanisms involved are not completely understood. In this sense, previous studies identified cholinergic terminals within the mPFC, and stressful stimuli increased local acetylcholine release. Despite these pieces of evidence, the specific role of cholinergic neurotransmission in different subregions of the mPFC controlling the cardiovascular responses to stress has never been systematically evaluated. Therefore, the purpose of this study was to investigate the involvement of cholinergic neurotransmission present within PL and IL in cardiovascular responses to an acute session of restraint stress in rats. For this, rats received bilateral microinjection of the choline uptake inhibitor hemicholinium-3 before exposure to restraint stress. The arterial pressure and heart rate (HR) increases and the decrease in tail skin temperature as an indirect measurement of sympathetically-mediated cutaneous vasoconstriction were recorded throughout the restraint stress session. The results showed that the depletion of acetylcholine within the PL caused by local microinjection of hemicholinium-3 decreased the tachycardia to restraint stress, but without affecting the pressor response and the drop in tail skin temperature. Conversely, IL treatment with hemicholinium-3 decreased the restraint-evoked pressor response and the sympathetically-mediated cutaneous vasoconstriction without interfering with the HR response. Taken together, these results indicate functional differences of cholinergic neurotransmission within the PL and IL in control of cardiovascular and autonomic responses to stressful stimuli.

Early maternal separation alters the activation of stress-responsive brain areas in adulthood.

The expression of c-Fos protein has been extensively used as a marker of neuronal activation in response to stressful stimuli. Early maternal separation (MS) is a model of early life adversity that affects the responsiveness of the brain areas to stressors. Thus, this study examined the impact of early MS on activating stress-responsive areas in the brain of adult rats in response to physical (ether) or psychological (restraint) stressors. Male pups were divided for the MS or non-handled (NH) groups. The MS was carried out daily between the 2nd and 14th day of postnatal life and consisted in removing the dams from the cage for 180 min. The rats were then subjected to experimental protocols of restraint or ether exposure at 10-12 weeks old. The rats were anesthetized 90 min after exposure to the stressors, and their brains were prepared for immunohistochemical analysis of c-Fos immunoreactive (c-Fos-ir) neurons in the hypothalamic paraventricular nucleus (PVN), supraoptic nucleus (SON), medial preoptic area (MPA), medial amygdaloid nucleus (MeA), locus coeruleus (LC), and nucleus of the solitary tract (NST). The MS-group presented 86%, 125%, 73%, 56%, and 137% higher c-Fos-ir neurons in the LC, PVN, SON, MPA, and MeA, respectively, compared to NH-group in response to the restraint stressor. In addition, the MS-group presented 180%, 137%, 170%, and 138% higher c-Fos-ir neurons for the ether exposure in the LC, PVN, MPA, and MeA, respectively. Our results show a greater increase in neuronal activation in the MS group, indicating that early life adversity can induce reprogramming in the brain response to stress in adulthood.

Stress levels of mangalita, large white, and pietrain pigs reared in different housing systems in south eastern Europe / Níveis de estresse de mangalita, grandes porcos brancos e pietrain criados em diferentes sistemas de alojamento no sudeste europeu

Cortisol is a steroid hormone that regulates a wide range of vital processes throughout the body, including metabolism and the immune response. It also has a very important role in helping the body respond to stress. Numerous studies have been conducted around the world to compare the development rates of pigs raised indoors to those raised outdoors, but the results have been ambiguous and, in many cases, conflicting. The objective of this study was to determine the effects of various housing systems (indoors with no free access to outdoor runs or indoors with free access to outdoor runs) on stress levels and slaughter value in growing-finishing pigs.

O cortisol é um hormônio esteroide que regula uma ampla gama de processos vitais em todo o corpo, incluindo o metabolismo e a resposta imune. Ele também tem um papel muito importante em ajudar o corpo a responder ao estresse. Numerosos estudos foram realizados em todo o mundo para comparar as taxas de desenvolvimento de porcos criados em ambientes fechados com aqueles criados ao ar livre, mas os resultados foram ambíguos e, em muitos casos, conflitantes. O objetivo deste estudo foi determinar os efeitos de vários sistemas de alojamento (dentro de casa sem acesso livre a corridas ao ar livre ou dentro de casa com acesso livre a corridas ao ar livre) nos níveis de estresse e no valor de abate em suínos em crescimento e terminação.

Psychosocial stressors predict lower cardiovascular disease risk among Mexican-American adults living in a high-risk community: Findings from the Texas City Stress and Health Study.

The objective of this study was to examine the link between systemic and general psychosocial stress and cardiovascular disease (CVD) risk in a group of U.S. Latinos as a function of acculturation and education within the blended guiding conceptual framework of the biopsychosocial model of the stress process plus the reserve capacity model. We analyzed data from self-identifying Mexican-origin adults (n = 396, 56.9% female, Mage = 58.2 years, 55.5% < 12 years of education, 79% U.S.-born) from the Texas City Stress and Health Study. We used established measures of perceived stress (general stress), neighborhood stress and discrimination (systemic stress) to capture psychosocial stress, our primary predictor. We used the atherosclerotic CVD calculator to assess 10-year CVD risk, our primary outcome. This calculator uses demographics, cholesterol, blood pressure, and history of hypertension, smoking, and diabetes to compute CVD risk in the next 10 years. We also created an acculturation index using English-language use, childhood interaction, and preservation of cultural values. Participants reported years of education. Contrary to expectations, findings showed that higher levels of all three forms of psychosocial stress, perceived stress, neighborhood stress, and perceived discrimination, predicted lower 10-year CVD risk. Acculturation and education did not moderate the effects of psychosocial stress on 10-year CVD risk. Contextualized within the biopsychosocial and reserve capacity framework, we interpret our findings such that participants who accurately reported their stressors may have turned to their social networks to handle the stress, thereby reducing their risk for CVD. We highlight the importance of examining strengths within the sociocultural environment when considering cardiovascular inequities among Latinos.

Short Daily Exposure to Environmental Enrichment, Fluoxetine, or Their Combination Reverses Deterioration of the Coat and Anhedonia Behaviors with Differential Effects on Hippocampal Neurogenesis in Chronically Stressed Mice.

Depression is a neuropsychiatric disorder with a high impact on the worldwide population. To overcome depression, antidepressant drugs are the first line of treatment. However, pre-clinical studies have pointed out that antidepressants are not entirely efficacious and that the quality of the living environment after stress cessation may play a relevant role in increasing their efficacy. As it is unknown whether a short daily exposure to environmental enrichment during chronic stress and antidepressant treatment will be more effective than just the pharmacological treatment, this study analyzed the effects of fluoxetine, environmental enrichment, and their combination on depressive-associated behavior. Additionally, we investigated hippocampal neurogenesis in mice exposed to chronic mild stress. Our results indicate that fluoxetine reversed anhedonia. Besides, fluoxetine reversed the decrement of some events of the hippocampal neurogenic process caused by chronic mild stress. Conversely, short daily exposure to environmental enrichment changed the deterioration of the coat and anhedonia. Although, this environmental intervention did not produce significant changes in the neurogenic process affected by chronic mild stress, fluoxetine plus environmental enrichment showed similar effects to those caused by environmental enrichment to reverse depressive-like behaviors. Like fluoxetine, the combination reversed the declining number of Ki67, doublecortin, calretinin cells and mature newborn neurons. Finally, this study suggests that short daily exposure to environmental enrichment improves the effects of fluoxetine to reverse the deterioration of the coat and anhedonia in chronically stressed mice. In addition, the combination of fluoxetine with environmental enrichment produces more significant effects than those caused by fluoxetine alone on some events of the neurogenic process. Thus, environmental enrichment improves the benefits of pharmacological treatment by mechanisms that need to be clarified.

Lateral hypothalamus involvement in control of stress response by bed nucleus of the stria terminalis endocannabinoid neurotransmission in male rats.

The endocannabinoid neurotransmission acting via local CB1 receptor in the bed nucleus of the stria terminalis (BNST) has been implicated in behavioral and physiological responses to emotional stress. However, the neural network related to this control is poorly understood. In this sense, the lateral hypothalamus (LH) is involved in stress responses, and BNST GABAergic neurons densely innervate this hypothalamic nucleus. However, a role of BNST projections to the LH in physiological responses to stress is unknown. Therefore, using male rats, we investigated the role of LH GABAergic neurotransmission in the regulation of cardiovascular responses to stress by CB1 receptors within the BNST. We observed that microinjection of the selective CB1 receptor antagonist AM251 into the BNST decreased the number of Fos-immunoreactive cells within the LH of rats submitted to acute restraint stress. Treatment of the BNST with AM251 also enhanced restraint-evoked tachycardia. Nevertheless, arterial pressure increase and sympathetically-mediated cutaneous vasoconstriction to restraint was not affected by CB1 receptor antagonism within the BNST. The effect of AM251 in the BNST on restraint-evoked tachycardia was abolished in animals pretreated with the selective GABAA receptor antagonist SR95531 in the LH. These results indicate that regulation of cardiovascular responses to stress by CB1 receptors in the BNST is mediated by GABAergic neurotransmission in the LH. Present data also provide evidence of the BNST endocannabinoid neurotransmission as a mechanism involved in LH neuronal activation during stressful events.

Early-Life Stress Reprograms Stress-Coping Abilities in Male and Female Juvenile Rats.

Prenatal stress (PS) is a major risk factor for the development of emotional disorders in adulthood that may be mediated by an altered hypothalamic-pituitary-adrenal axis response to stress. Although the early onset of stress-related disorders is recognized as a major public health problem, to date, there are relatively few studies that have examined the incidence of early-life stressors in younger individuals. In this study, we assessed PS impact on the stress-coping response of juvenile offspring in behavioral tests and in the induced molecular changes in the hippocampus. Furthermore, we assessed if pregnancy stress could be driving changes in patterns of maternal behavior during early lactation. We found that PS modified stress-coping abilities of both sex offspring. In the hippocampus, PS increased the expression of bdnf-IV and crfr1 and induced sex difference changes on glucocorticoids and BDNF mRNA receptor levels. PS changed the hippocampal epigenetic landscape mainly in male offspring. Stress during pregnancy enhanced pup-directed behavior of stressed dams. Our study indicates that exposure to PS, in addition to enhanced maternal behavior, induces dynamic neurobehavioral variations at juvenile ages of the offspring that should be considered adaptive or maladaptive, depending on the characteristics of the confronting environment. Our present results highlight the importance to further explore risk factors that appear early in life that will be important to allow timely prevention strategies to later vulnerability to stress-related disorders.

Patterns of poverty across adolescence predict salivary cortisol stress responses in Mexican-origin youths.

Poverty is a chronic stressor associated with disruptions in psychophysiological development during adolescence. This study examined associations of chronic poverty and income changes experienced from pre- to mid-adolescence with hypothalamic-pituitary-adrenal (HPA) axis stress responses in late adolescence. Participants (N = 229) were adolescents of Mexican-origin (48.7% female). Household income (converted to income-to-needs ratios) was assessed annually when children were 10-16 years old. At 17 years, adolescents completed Cyberball, a social exclusion simulation task while undergoing a functional magnetic resonance imaging scan. Saliva samples were collected prior to and five times over a 50-minute period following the scan, from which salivary cortisol was assayed. Results showed that differential trajectories of poverty from ages 10-16 predicted HPA axis activity at age 17. Relative to others, distinct HPA suppression (hyporeactivity) was demonstrated by youth who started adolescence in deep poverty and were still living in poverty at age 16 despite experiencing some income gains. Youth from more economically secure families evinced typical cortisol increases following the lab stressor. These results suggest that subsequent HPA functioning varies as a function of economic status throughout adolescence, and that efforts to increase family income may promote healthy HPA functioning for youths in the most impoverished circumstances.

Stress, memory, and implications for major depression.

The stress response comprises a phylogenetically conserved set of cognitive, physiological, and behavioral responses that evolved as a survival strategy. In this context, the memory of stressful events would be adaptive as it could avoid re-exposure to an adverse event, otherwise the event would be facilitated in positively stressful or non-distressful conditions. However, the interaction between stress and memory comprises complex responses, some of them which are not yet completely understood, and which depend on several factors such as the memory system that is recruited, the nature and duration of the stressful event, as well as the timing in which this interaction takes place. In this narrative review, we briefly discuss the mechanisms of the stress response, the main memory systems, and its neural correlates. Then, we show how stress, through the action of its biochemical mediators, influences memory systems and mnemonic processes. Finally, we make use of major depressive disorder to explore the possible implications of non-adaptive interactions between stress and memory to psychiatric disorders, as well as possible roles for memory studies in the field of psychiatry.

The Role of HPA Axis and Allopregnanolone on the Neurobiology of Major Depressive Disorders and PTSD.

Under stressful conditions, the hypothalamic-pituitary-adrenal (HPA) axis acts to promote transitory physiological adaptations that are often resolved after the stressful stimulus is no longer present. In addition to corticosteroids (e.g., cortisol), the neurosteroid allopregnanolone (3α,5α-tetrahydroprogesterone, 3α-hydroxy-5α-pregnan-20-one) participates in negative feedback mechanisms that restore homeostasis. Chronic, repeated exposure to stress impairs the responsivity of the HPA axis and dampens allopregnanolone levels, participating in the etiopathology of psychiatric disorders, such as major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). MDD and PTSD patients present abnormalities in the HPA axis regulation, such as altered cortisol levels or failure to suppress cortisol release in the dexamethasone suppression test. Herein, we review the neurophysiological role of allopregnanolone both as a potent and positive GABAergic neuromodulator but also in its capacity of inhibiting the HPA axis. The allopregnanolone function in the mechanisms that recapitulate stress-induced pathophysiology, including MDD and PTSD, and its potential as both a treatment target and as a biomarker for these disorders is discussed.

Angiotensinergic Neurotransmissions in the Medial Amygdala Nucleus Modulate Behavioral Changes in the Forced Swimming Test Evoked by Acute Restraint Stress in Rats.

We investigated the role of angiotensin II type 1 (AT1 receptor) and type 2 (AT2 receptor) and MAS receptors present in the medial amygdaloid nucleus (MeA) in behavioral changes in the forced swimming test (FST) evoked by acute restraint stress in male rats. For this, rats received bilateral microinjection of either the selective AT1 receptor antagonist losartan, the selective AT2 receptor antagonist PD123319, the selective MAS receptor antagonist A-779, or vehicle 10 min before a 60 min restraint session. Then, behavior in the FST was evaluated immediately after the restraint (15 min session) and 24 h later (5 min session). The behavior in the FST of a non-stressed group was also evaluated. We observed that acute restraint stress decreased immobility during both sessions of the FST in animals treated with vehicle in the MeA. The decreased immobility during the first session was inhibited by intra-MeA administration of PD123319, whereas the effect during the second session was not identified in animals treated with A-779 into the MeA. Microinjection of PD123319 into the MeA also affected the pattern of active behaviors (i.e., swimming and climbing) during the second session of the FST. Taken together, these results indicate an involvement of angiotensinergic neurotransmissions within the MeA in behavioral changes in the FST evoked by stress.