Stress-related Behaviors Research Articles

Effect of camel’s previous experience on behavioural response and milk production during training to machine milking

At the onset of lactation, dairy animals are exposed to novel stimuli within the mechanical milking environment, which can induce stress. This is particularly pronounced in camels due to their sensitive and potentially maternal aggressive nature. To propose strategies to reduce these stress, this study aimed to assess the behavioural and milking responses of dairy camels during their first milking sessions with a focus on the influence of dams’ experience. Eleven dairy camels were included in this study, with 5 undergoing their inaugural milking season (designated as the N_Exp group) and 6 camels having prior exposure to machine milking during previous lactations (designated as the Exp group). Camels were milked with an individual portable milking machine set to 48 kPa Vacuum and 60 pulsations/min. Throughout this trial, behavioural data, rumination occurrence, need of oxytocin injection to induce milk ejection, milk yield, time to milk ejection and milking duration were recorded during the 3 weeks training period of camels. A training index (T.I.) was calculated to quantify milking adaptation from behavioural responses. Stress-related behaviours were classified into fear-related behaviours such as jumping, decubitus, trembling, vocalization and escape attempts) as well as defensive behaviours including kicking, stepping, spitting, and biting. Results showed that N Exp camels expressed fear-related behaviours more frequently (P < 0.05) while displaying a lower training index (P < 0.0001) compared to Exp camels. All stress behaviours decreased significantly throughout the training period for both groups. The need for exogenous oxytocin decreased from 100% at the first day of machine milking to 35% for N_Exp group and from 27.8% to 8.3% for Exp group. The camel’s experience had no effect (p = 0.4200) on the rumination frequency. However, rumination occurred more and more frequently (P < 0.0001) during the camels’ training period. Time to milk ejection, total and effective milking durations were significantly shorter for experienced camels and reduced throughout the camels’ training period (P< 0.0001). Milk production increased gradually for both groups by 71.75% and 61.83% for Exp and N_Exp respectively during camels’ training period. In conclusion, acclimation of camels to machine milking was accompanied by a reduction of acute stress behaviours occurrences, an increase in milk production and a shortening and normalisation of milking sessions. Experienced camels were easier to train to machine milking. These results underscore the importance of improving procedures of milking habituation to mitigate stress of the first milking session and improve the welfare of dairy camels.

Mitochondrial morphology in the mouse adrenal cortex: Influence of chronic psychosocial stress

Mitochondria within the adrenal cortex play a key role in synthesizing steroid hormones. The adrenal cortex is organized in three functionally specialized zones (glomerulosa, fasciculata, and reticularis) that produce different classes of steroid hormones in response to various stimuli, including psychosocial stress. Given that the functions and morphology of mitochondria are dynamically related and respond to stress, we applied transmission electron microscopy (TEM) to examine potential differences in mitochondrial morphology under basal and chronic psychosocial stress conditions. We used the chronic subordinate colony housing (CSC) paradigm, a murine model of chronic psychosocial stress. Our findings quantitatively define how mitochondrial morphology differs among each of the three adrenal cortex zones under basal conditions, and show that chronic psychosocial stress mainly affected mitochondria in the zona glomerulosa, shifting their morphology towards the more typical glucocorticoid-producing zona fasciculata mitochondrial phenotype. Analysis of adrenocortical lipid droplets that provide cholesterol for steroidogenesis showed that chronic psychosocial stress altered lipid droplet diameter, without affecting droplet number or inter-organellar mitochondria-lipid droplet interactions. Together, our findings support the hypothesis that each adrenal cortex layer is characterized by morphologically distinct mitochondria and that this adrenal zone-specific mitochondrial morphology is sensitive to environmental stimuli, including chronic psychosocial stressors. Further research is needed to define the role of these stress-induced changes in mitochondrial morphology, particularly in the zona glomerulosa, on stress resilience and related behaviors.

Mitochondrial fission drives neuronal metabolic burden to promote stress susceptibility in male mice.

Neurons are particularly susceptible to energy fluctuations in response to stress. Mitochondrial fission is highly regulated to generate ATP via oxidative phosphorylation; however, the role of a regulator of mitochondrial fission in neuronal energy metabolism and synaptic efficacy under chronic stress remains elusive. Here, we show that chronic stress promotes mitochondrial fission in the medial prefrontal cortex via activating dynamin-related protein 1 (Drp1), resulting in mitochondrial dysfunction in male mice. Both pharmacological inhibition and genetic reduction of Drp1 ameliorates the deficit of excitatory synaptic transmission and stress-related depressive-like behavior. In addition, enhancing Drp1 fission promotes stress susceptibility, which is alleviated by coenzyme Q10, which potentiates mitochondrial ATP production. Together, our findings unmask the role of Drp1-dependent mitochondrial fission in the deficits of neuronal metabolic burden and depressive-like behavior and provides medication basis for metabolism-related emotional disorders.

CHL1 depletion affects dopamine receptor D2-dependent modulation of mouse behavior.

The dopaminergic system plays a key role in the appropriate functioning of the central nervous system, where it is essential for emotional balance, arousal, reward, and motor control. The cell adhesion molecule close homolog of L1 (CHL1) contributes to dopaminergic system development, and CHL1 and the dopamine receptor D2 (D2R) are associated with mental disorders like schizophrenia, addiction, autism spectrum disorder and depression. Here, we investigated how the interplay between CHL1 and D2R affects the behavior of young adult male and female wild-type (CHL+/+) and CHL1-deficient (CHL1-/-) mice, when D2R agonist quinpirole and antagonist sulpiride are applied. Low doses of quinpirole (0.02 mg/kg body weight) induced hypolocomotion of CHL1+/+ and CHL1-/- males and females, but led to a delayed response in CHL1-/- mice. Sulpiride (1 mg/kg body weight) affected locomotion of CHL1-/- females and social interaction of CHL1+/+ females as well as social interactions of CHL1-/- and CHL1+/+ males. Quinpirole increased novelty-seeking behavior of CHL1-/- males compared to CHL1+/+ males. Vehicle-treated CHL1-/- males and females showed enhanced working memory and reduced stress-related behavior. We propose that CHL1 regulates D2R-dependent functions in vivo. Deficiency of CHL1 leads to abnormal locomotor activity and emotionality, and to sex-dependent behavioral differences.

PSIX-1 Impact of a Botanical Blend on Training Kennel Induced Stress in Dogs

Abstract Fear and anxiety in dogs can be elevated during transportation or visits to the veterinarian, groomer, and boarding or training kennels. The stress-related behaviors exhibited during these times can be a welfare concern to both pet, handler, and owner. In the case of training or grooming, the productivity of the session may be reduced due to unwanted stress related behaviors. Pet owners want to reduce stress during these events and are seeking natural botanical alternatives to medications. The botanical extracts in Cani-Calm (Probiotech International, Inc.) successfully decreased stress-related behaviors when fed to beagles for 11 days before a novel 1-hr car ride stress test. There has not been any investigation into the impact of these botanicals during a prolonged stress event similar to a boarding or training kennel. The objective was to evaluate Cani-Calm when offered during a 3-week training program at a boarding kennel. Fifty-one dogs of various ages, breed, and history were randomly assigned to either Control (no Cani-Calm; n = 26) or Cani-Calm (CC: 0.6 mL· kg BWT-1· day-1; n = 25). Cani-Calm was top-dressed on the morning meal daily. Trainers, blinded to treatment, assessed dog behavior and provided training timelines for each dog. Statistical analysis was performed using a Genmod analysis and Poisson distribution in SAS v9.3. Statistical significance was set at P &amp;lt; 0.05 and statistical trends were considered at 0.05 &amp;lt; P &amp;lt; 0.10. Length of the acclimation period before the onset of training due to stress-related behaviors was reduced (P = 0.001) in treated dogs compared with the control (Control: 1.57± 0.16 d; CC: 0.08 ± 0.71 d). There was no impact of treatment (P = 0.15) on percentage of dogs per group that required additional days of training beyond the planned program. However, there was an impact of treatment (P = 0.04; Control: 75%; CC: 96.3%) on the percentage of dogs that completed training earlier than the scheduled 3-week program. The results indicate a benefit of Cani-Calm during stressful events to decrease the display of behaviors that reduce training productivity and are a welfare concern for both animal and handler. Unlike the previous trial, during the current trial, there was no exposure to the botanicals before the stressful event; however, alterations in stress-related behaviors were demonstrated in both trials. Further research is warranted to evaluate time of exposure to the botanicals before the stress-event, and in larger populations.

Study on Heat Stress Behavior and Blood H/L Ratio of Ducks Fed Diets Containing Mix Strains of Probiotics in Commercial Farms

An experiment has been conducted with the purpose of examining the effect of two kinds of probiotic on the behavior and blood H/L ratio of local ducks kept in commercial farms. The study was conducted in collaboration with the ‘Berkah Abadi’ duck farmer group which keeps the bird under an intensive dry system. The intensive system refers to the ordinary way done by the farmers in which ducks were confined around the farmer’s village with a closed fence so the birds had no access to the outside area, and the amount of feed provided could be controlled and measured. The location was in the coastal area of Tegal City as one of the most famous duck centers in Indonesia. The materials used were 13.4+1.3 months old local laying ducks which were reared by the farmer group. The study used a Completely Randomized Design with treatments consisting of 3 doses of P and P+ probiotics respectively. P contained Lactobacillus sp. combined with Saccharomyces cerevisiae, whereas P+ comprised Lactobacillus sp., Saccharomyces cerevisiae, Streptococcus thermophilus, and Lactobacillus bulgaricus. There were 6 treatment units which were replicated 4 times, so in total there were 24 flocks. Each flock had 50 female ducks; therefore this study involved 1,200 ducks. The treatments were applied each morning, and mixed thoroughly in duck ration. Data collected were heat stress-related behavior, body temperature, and H/L ratio. It was concluded that P and P+ had similar effects on the behaviour and H/L ratio of local ducks kept under commercial management.

Sex differences in androgen receptor, estrogen receptor alpha, and c-Fos co-expression with corticotropin releasing factor expressing neurons in restrained adult mice

Gonadal hormone actions through androgen receptor (AR) and estrogen receptor alpha (ERα) regulate sex differences in hypothalamic-pituitary-adrenal (HPA) axis responsivity and stress-related behaviors. Here we tested whether corticotropin releasing factor (CRF) expressing neurons, which are widely known to regulate neuroendocrine and behavioral stress responses, co-express AR and ERα as a potential mechanism for gonadal hormone regulation of these responses. Using Crh-IRES-Cre::Ai9 reporter mice we report high co-localization of AR in CRF neurons within the medial preoptic area (MPOA), bed nucleus of the stria terminalis (BST), medial amygdala (MeA), and ventromedial hypothalamus (VMH), moderate levels within the central amygdala (CeA) and low levels in the paraventricular hypothalamus (PVN). Sex differences in CRF/AR co-expression were found in the principal nucleus of the BST (BSTmpl), CeA, MeA, and VMH (males>females). CRF co-localization with ERα was generally lower relative to AR co-localization. However, high co-expression was found within the MPOA, AVPV, and VMH, with moderate co-expression in the arcuate nucleus (ARC), BST, and MeA and low levels in the PVN and CeA. Sex differences in CRF/ERα co-localization were found in the BSTmpl and PVN (males>females). Finally, we assessed neural activation of CRF neurons in restraint-stressed mice and found greater CRF/c-Fos co-expression in females in the BSTmpl and periaqueductal gray, while co-expression was higher in males within the ARC and dorsal CA1. Given the known role of CRF in regulating behavioral stress responses and the HPA axis, AR/ERα co-expression and sex-specific activation of CRF cell groups indicate potential mechanisms for modulating sex differences in these functions.

The pleiotropic contribution of genes in dopaminergic and serotonergic pathways to addiction and related behavioral traits.

Co-occurrence of substance use disorders (SUD) and other behavioral conditions, such as stress-related, aggressive or risk-taking behaviors, in the same individual has been frequently described. As dopamine (DA) and serotonin (5-HT) have been previously identified as key neurotransmitters for some of these phenotypes, we explored the genetic contribution of these pathways to SUD and these comorbid phenotypes in order to better understand the genetic relationship between them. We tested the association of 275 dopaminergic genes and 176 serotonergic genes with these phenotypes by performing gene-based, gene-set and transcriptome-wide association studies in 11 genome-wide association studies (GWAS) datasets on SUD and related behaviors. At the gene-wide level, 68 DA and 27 5-HT genes were found to be associated with at least one GWAS on SUD or related behavior. Among them, six genes had a pleiotropic effect, being associated with at least three phenotypes: ADH1C, ARNTL, CHRNA3, HPRT1, HTR1B and DRD2. Additionally, we found nominal associations between the DA gene sets and SUD, opioid use disorder, antisocial behavior, irritability and neuroticism, and between the 5-HT-core gene set and neuroticism. Predicted gene expression correlates in brain were also found for 19 DA or 5-HT genes. Our study shows a pleiotropic contribution of dopaminergic and serotonergic genes to addiction and related behaviors such as anxiety, irritability, neuroticism and risk-taking behavior, highlighting a role for DA genes, which could explain, in part, the co-occurrence of these phenotypes.

Adolescent alcohol disrupts development of noradrenergic neurons in the nucleus of the tractus solitarius and enhances stress behaviors in adulthood in mice in a sex specific manner

Alcohol use disorders (AUDs) are common mental health issues worldwide and can lead to other chronic diseases. Stress is a major factor in the development and continuation of AUDs, and adolescent alcohol exposure can lead to enhanced stress-responsivity and increased risk for AUD development in adulthood. The exact mechanisms behind the interaction between adolescence, stress, and alcohol are not fully understood and require further research. In this regard, the nucleus of the tractus solitarius (NTS) provides dense norepinephrine projections to the extended amygdala, providing a key pathway for stress-related alcohol behaviors. While NTS norepinephrine neurons are known to be alcohol sensitive, whether adolescent alcohol disrupts NTS-norepinephrine neuron development and if this is related to altered stress-sensitivity and alcohol preference in adulthood has not previously been examined. Here, we exposed male and female C57Bl/6J mice to the commonly used adolescent intermittent ethanol (AIE) vapor model during postnatal day 28-42 and examined AIE effects on: 1) tyrosine hydroxylase (TH) mRNA expression in the NTS across various ages (postnatal day 21-90), 2) behavioral responses to acute stress in the light/dark box test in adulthood, 3) NTS TH neuron responses to acute stress and ethanol challenges in adulthood, and 4) ethanol conditioned place preference behavior in adulthood. Overall the findings indicate that AIE alters NTS TH mRNA expression and increases anxiety-like behaviors following acute stress exposure in a sex-dependent manner. These mRNA expression and behavioral changes occur in the absence of AIE-induced changes in NTS TH neuron sensitivity to either acute stress or acute alcohol exposure or changes to ethanol conditioned place preference.

Identifying potential measures of stress and disturbance during a captive to wild African elephant reintegration.

There is increasing evidence of compromised welfare for elephants managed in captivity. Should such facilities eventually close, more elephants will need to be rehabilitated and reintegrated into the wild. The goal of such reintegration would be to restore any physical or psychological aspects of the elephant that may have been compromised in captivity, followed by introduction into a free-roaming system where they can interact with other elephants. However, to achieve this goal, the reintegration methods implemented need to be assessed to ensure that welfare remains the priority. The objective of this study was to test whether parameters generally associated with stress and disturbance in African elephants, respond to changes in potentially stressful environmental conditions, assessed at multiple temporal scales ranging from minutes to months. The main changes in environmental conditions that were investigated included the different phases of reintegration of a group of elephants from captivity into the wild. Stress and disturbance related parameters used for comparisons included physiological responses, namely the extent of temporal gland secretions (eTGS) and faecal glucocorticoid metabolite (fGCM) levels as well as behavioural responses, namely the display of stereotype and stress-related behaviours. Results showed that eTGS significantly increased during the initial release of the elephants compared to when in captivity. Stereotypic behaviours were only recorded during the captive phase and immediately ceased after release. Faecal GCM levels spiked in the first year after release before decreasing back to pre-reintegration levels during the third year. These findings indicate that fGCM levels, the eTGS and disturbance related behaviours all proved effective in explaining the changes in stress and disturbance experienced by elephants during the initial years after being reintegrated from captivity into the wild.

Assessing Negative Welfare Measures for Wild Invertebrates: The Case for Octopuses.

Welfare metrics have been established for octopuses in the laboratory, but not for octopuses living in the wild. Wild octopuses are constantly exposed to potentially harmful situations, and the ability to assess the welfare status of wild octopuses could provide pertinent information about individuals' health and species' resilience to stressors. Here, we used underwater photos and videos to identify injuries and stress-related behaviors in wild Octopus insularis in a variety of contexts, including interacting with fishermen, interacting with other octopuses and fish, proximity to predators, in den, foraging, and in senescence. We adapted established metrics of octopus welfare from the laboratory to these wild octopuses. In addition to observing all of the stress measures, we also identified two previously unknown measures associated with decreased welfare: (1) a half white eye flash and (2) a half-and-half blotch body pattern. More than half of the individuals analyzed had arm loss, and almost half of the individuals had skin injuries. We also observed that irregular chromatophore expression and abnormal motor coordination were associated with interactions with fishermen. This is the first study to apply measures of welfare from the laboratory to wild octopuses. Our results may also aid in the identification of welfare measures for other wild invertebrates.

Behavior of Mothers after Infant Loss in Bonnet Macaques (Macaca radiata)

Mother–offspring bonds in primates often last for life and shape the behavior of both mother and offspring. Therefore, the death of an infant may trigger an emotional response from its mother akin to human grief, which is characterized by active distress and passive depression. Our goal was to investigate whether the behavior of female bonnet macaques (Macaca radiata) changed after the loss of their infants. In the Thenmala area, southern India, between 2020 and 2022, we observed 18 mothers in two groups who lost, in total, 19 infants and three juveniles aged < 18 months. We compared affiliative, aggressive, and stress-related behavior of females before and after the death of their infants. We also examined individual variation in responses to infant loss. After the death of their infants, females withdrew socially, stayed on the periphery of the group, and had fewer companions. Bereaved females were less involved in grooming and hugging and initiated aggressive behavior more frequently than before they lost their infants. Moreover, females who lost infants showed frequent stress-related behaviors, such as self-scratching and yawning compared with when their infants were alive. Our results suggest that female bonnet macaques react to deaths of their infants in a manner that is consistent with the interpretation of grief in humans and other primates.

Clinical and psychological aspects in a group of allergic asthma patients and the impact on their health status perception.

The interplay between physical and psychological symptoms frequently affects the health-related quality of life of asthma patients. This research aimed at assessing the psychological status of 60 patients attending their first/second doctor visit at which they were diagnosed with allergic asthma. Information on psychological distress was collected through the Symptom Questionnaire (SQ), personality traits were described through Cattell's 16-Personality Factor Questionnaire (16-PF), stress-related behavior was detected through the P Stress Questionnaire (PSQ), and the perceived quality of life was described with the Rhinasthma questionnaire. The SQ revealed anxiety levels above the clinical cut-off in 71.7% of patients, levels of depression in 46.7%, anger-hostility in 53.3%, and somatic symptoms in 65%. No significant differences were observed after three months. The 16-PF scores were also suggestive of specific personality traits associated with the predisposition towards psychosomatic disorders. However, no stress-related behaviors were observed with the PSQ. Rhinasthma highlighted a certain degree of the perceived quality of life. Additionally, the quality of life correlated with age, all psychological distress scales, a few personality traits, vigor, and stress disorders. Allergic asthma patients present a higher-than-average level of psychological distress and impaired perceived quality of life at the time of diagnosis. Therefore, it is important to assess the psychological status in addition to the respiratory function.

The effect of COVID-19 anxiety and awareness on smoking urges: the moderator effect of demographic factors

ABSTRACT Objective This study aimed to examine the impact of COVID-19 awareness and COVID-19 anxiety on smoking urges, while considering the potential moderating effects of socio-demographic factors. Methods A cross-sectional analysis was conducted to assess the relationships between COVID-19 awareness, COVID-19 anxiety, and smoking urges. The study also explored how factors such as age, income level, and chronic disease might moderate these relationships. Statistical analysis included regression modeling to determine the strength and significance of the associations. Results The findings indicate that COVID-19 anxiety has a negative impact on smoking urges at a low level (β = -0.135; p < 0.01), while COVID-19 awareness moderately and negatively influences smoking urges (β = -0.558; p < 0.001). Furthermore, the study identified that age, income level, and chronic disease act as moderators in the relationship between COVID-19 anxiety, COVID-19 awareness, and smoking urges. Specifically, the effects of COVID-19 anxiety and awareness on smoking urges are amplified among individuals who are older, have a higher income, and experience chronic illness. Conclusion The study highlights the significance of COVID-19 awareness in reducing smoking urges among individuals. It also emphasizes that while COVID-19 anxiety diminishes smoking urges to a certain extent, it might paradoxically trigger stress-related smoking behaviors. Importantly, the impact of both awareness and anxiety on smoking urges is more pronounced in individuals who are older, have a higher income, and suffer from chronic diseases. These findings underscore the complex interplay between psychological factors, awareness, and socio-demographic characteristics in influencing smoking behaviors during the COVID-19 pandemic.

Numerical Modeling of Physical Cell Trapping in Microfluidic Chips.

Microfluidic methods have proven to be effective in separation and isolation of cells for a wide range of biomedical applications. Among these methods, physical trapping is a label-free isolation approach that relies on cell size as the selective phenotype to retain target cells on-chip for follow-up analysis and imaging. In silico models have been used to optimize the design of such hydrodynamic traps and to investigate cancer cell transmigration through narrow constrictions. While most studies focus on computational fluid dynamics (CFD) analysis of flow over cells and/or pillar traps, a quantitative analysis of mechanical interaction between cells and trapping units is missing. The existing literature centers on longitudinally extended geometries (e.g., micro-vessels) to understand the biological phenomenon rather than designing an effective cell trap. In this work, we aim to make an experimentally informed prediction of the critical pressure for a cell to pass through a trapping unit as a function of cell morphology and trapping unit geometry. Our findings show that a hyperelastic material model accurately captures the stress-related softening behavior observed in cancer cells passing through micro-constrictions. These findings are used to develop a model capable of predicting and extrapolating critical pressure values. The validity of the model is assessed with experimental data. Regression analysis is used to derive a mathematical framework for critical pressure. Coupled with CFD analysis, one can use this formulation to design efficient microfluidic devices for cell trapping and potentially perform downstream analysis of trapped cells.

Repeated witness social stress causes cardiomyocyte contractile impairment and intracellular Ca2+ derangement in female rats

The impact of psychosocial stressors on cardiovascular health in women is of growing interest in both the popular and scientific literature. Rodent models are useful for providing direct experimental evidence of the adverse cardiovascular consequences of psychosocial stressors, yet studies in females are scarce. Here, we investigated the effects of repeated exposure to witness social defeat stress (WS) on cardiomyocyte contractile function and intracellular Ca2+ homeostasis in young adult wild-type Groningen female rats. Female rats bore witness to an aggressive social defeat episode between two males for nine consecutive days or were exposed to a control procedure. Stress-related behaviors were assessed during the first and last WS/control exposure. Twenty-four hours after the last exposure, plasma corticosterone levels were measured, and cardiomyocytes were isolated for analyses of contractile properties and Ca2+ transients, and expression levels of proteins involved in intracellular Ca2+dynamics. The results show an impairment of the intrinsic cardiac mechanical properties and prolonged intracellular Ca2+decay in WS female rats showing social stress-related behavioral (larger amounts of burying behavior) and neuroendocrine (elevated plasma corticosterone levels) phenotypes. Further, the results implicate alterations in the sarcoplasmic reticulum Ca2+-ATPase/phospholamban complex in the contractile defects described in cardiomyocytes of WS female rats. In conclusion, this study highlights the utility of the WS model as an ethologically relevant social stressor for investigating pathophysiological processes that occur in the heart of female subjects and may increase vulnerability to social stress-related cardiovascular risk.

Sexually dimorphic effects of monoacylglycerol lipase inhibitor MJN110 on stress-related behaviour and drinking in Marchigian Sardinian alcohol-preferring rats.

The endocannabinoid (eCB) system plays an important homeostatic role in the regulation of stress circuits and has emerged as a therapeutic target to treat stress disorders and alcohol use disorder (AUD). Extensive research has elucidated a role for the eCB anandamide (AEA), but less is known about 2-arachidonoylglycerol (2-AG) mediated signalling. We pharmacologically enhanced eCB signalling by inhibiting the 2-AG metabolizing enzyme, monoacylglycerol lipase (MAGL), in male and female Marchigian Sardinian alcohol-preferring (msP) rats, a model of innate alcohol preference and stress hypersensitivity, and in control Wistar rats. We tested the acute effect of the selective MAGL inhibitor MJN110 in alleviating symptoms of alcohol drinking, anxiety, irritability and fear. A single systemic administration of MJN110 increased 2-AG levels in the central amygdala, prelimbic and infralimbic cortex but did not acutely alter alcohol drinking. MAGL inhibition reduced aggressive behaviours in female msPs, and increased defensive behaviours in male msPs, during the irritability test. Moreover, in the novelty-induced hypophagia test, MJN110 selectively enhanced palatable food consumption in females, mitigating stress-induced food suppression. Lastly, msP rats showed increased conditioned fear behaviour compared with Wistar rats, and MJN110 reduced context-associated conditioned fear responses, but not cue-probed fear expression, in male msPs. Acute inhibition of MAGL attenuated some stress-related responses in msP rats but not voluntary alcohol drinking. Our results provide new insights into the sex dimorphism documented in stress-induced responses. Sex-specific eCB-based approaches should be considered in the clinical development of therapeutics.

Sex-specific effects of psychoactive pollution on behavioral individuality and plasticity in fish.

The global rise of pharmaceutical contaminants in the aquatic environment poses a serious threat to ecological and evolutionary processes. Studies have traditionally focused on the collateral (average) effects of psychoactive pollutants on ecologically relevant behaviors of wildlife, often neglecting effects among and within individuals, and whether they differ between males and females. We tested whether psychoactive pollutants have sex-specific effects on behavioral individuality and plasticity in guppies (Poecilia reticulata), a freshwater species that inhabits contaminated waterways in the wild. Fish were exposed to fluoxetine (Prozac) for 2 years across multiple generations before their activity and stress-related behavior were repeatedly assayed. Using a Bayesian statistical approach that partitions the effects among and within individuals, we found that males-but not females-in fluoxetine-exposed populations differed less from each other in their behavior (lower behavioral individuality) than unexposed males. In sharp contrast, effects on behavioral plasticity were observed in females-but not in males-whereby exposure to even low levels of fluoxetine resulted in a substantial decrease (activity) and increase (freezing behavior) in the behavioral plasticity of females. Our evidence reveals that psychoactive pollution has sex-specific effects on the individual behavior of fish, suggesting that males and females might not be equally vulnerable to global pollutants.

Brain mitochondrial diversity and network organization predict anxiety-like behavior in male mice

The brain and behavior are under energetic constraints, limited by mitochondrial energy transformation capacity. However, the mitochondria-behavior relationship has not been systematically studied at a brain-wide scale. Here we examined the association between multiple features of mitochondrial respiratory chain capacity and stress-related behaviors in male mice with diverse behavioral phenotypes. Miniaturized assays of mitochondrial respiratory chain enzyme activities and mitochondrial DNA (mtDNA) content were deployed on 571 samples across 17 brain areas, defining specific patterns of mito-behavior associations. By applying multi-slice network analysis to our brain-wide mitochondrial dataset, we identified three large-scale networks of brain areas with shared mitochondrial signatures. A major network composed of cortico-striatal areas exhibited the strongest mitochondria-behavior correlations, accounting for up to 50% of animal-to-animal behavioral differences, suggesting that this mito-based network is functionally significant. The mito-based brain networks also overlapped with regional gene expression and structural connectivity, and exhibited distinct molecular mitochondrial phenotype signatures. This work provides convergent multimodal evidence anchored in enzyme activities, gene expression, and animal behavior that distinct, behaviorally-relevant mitochondrial phenotypes exist across the male mouse brain.

Partner-seeking and limbic dopamine system are enhanced following social loss in male prairie voles (Microtus ochrogaster).

Death of a loved one is recognized as one of life's greatest stresses, and 10%-20% of bereaved individuals will experience a complicated or prolonged grieving period that is characterized by intense yearning for the deceased. The monogamous prairie vole (Microtus ochrogaster) is a rodent species that forms pair bonds between breeding partners and has been used to study the neurobiology of social behaviors and isolation. Male prairie voles do not display distress after isolation from a familiar, same-sex conspecific; however, separation from a bonded female partner increases emotional, stress-related, and proximity-seeking behaviors. Here, we tested the investigatory response of male voles to partner odor during a period of social loss. We found that males who lost their partner spent significantly more time investigating partner odor but not non-partner social odor or food odor. Bachelor males and males in intact pairings did not respond uniquely to any odor. Furthermore, we examined dopamine (DA) receptor mRNA expression in the anterior insula cortex (aIC), nucleus accumbens (NAc), and anterior cingulate (ACC), regions with higher activation in grieving humans. While we found some effects of relationship type on DRD1 and DRD2 expression in some of these regions, loss of a high-quality opposite-sex relationship had a significant effect on DA receptor expression, with pair-bonded/loss males having higher expression in the aIC and ACC compared with pair-bonded/intact and nonbonded/loss males. Together, these data suggest that both relationship type and relationship quality affect reunion-seeking behavior and motivational neurocircuits following social loss of a bonded partner.