Anxiolytic and Antianhedonic-like Effects of Psidium guajava Leaf in Alcohol-Withdrawn Mice.

Objectives: Alcohol withdrawal syndrome manifests through a range of symptoms, including anxiety and anhedonia, significantly affecting the quality of life of those affected. This study investigates the potential therapeutic effects of the methanolic extract of Psidium guajava leaves (MPG) on anxiety and anhedonia in Swiss albino female mice undergoing alcohol withdrawal. Methods: Four groups of mice underwent alcohol withdrawal, with one group undergoing saline withdrawal as a control. On the test day, behavioral assessments were conducted to evaluate anxiety and anhedonia. Groups I and II received sodium carboxymethylcellulose, Group III received diazepam, and Groups IV and V received varying oral doses of MPG. Results: The results indicate significant anti-anhedonic and anxiolytic effects of MPG. These effects were observed through changes in parameters measured in the Open Field test, Elevated Plus Maze test, Marble Burying test, and Sucrose Preference test. Mice treated with MPG displayed reduced anxiety-like behaviors and increased sucrose preference compared to untreated mice undergoing alcohol withdrawal. Conclusion: These findings suggest that Psidium guajava leaf extract may have therapeutic potential in alleviating anxiety and anhedonia associated with alcohol withdrawal. The observed effects indicate that MPG could serve as a promising adjunct therapy for managing alcohol withdrawal symptoms, thereby enhancing the overall well-being of individuals undergoing alcohol cessation.

Repeated Administration of a Full-Spectrum Cannabidiol Product, Not a Cannabidiol Isolate, Reverses the Lipopolysaccharide-Induced Depressive-Like Behavior and Hypolocomotion in a Rat Model of Low-Grade Subchronic Inflammation.

Background: Mounting evidence suggests that the phytocannabinoid cannabidiol (CBD) holds promise as an antidepressant agent in conditions underlined by inflammation. Full-spectrum CBD extracts might provide greater behavioral efficacy than CBD-only isolates and might require lower doses to achieve the same outcomes due to the presence of other cannabinoids, terpenes, and flavonoids. However, investigations in this area remain limited. Methods: We evaluated the behavioral response to the administration for 7 days of 15 and 30 mg/kg of a CBD isolate and a full-spectrum CBD product in a rat model of subchronic lipopolysaccharide (LPS, 0.5 mg/kg/day/7 days, intraperitoneal)-induced depressive-like and sickness behavior. The forced swim test was used to assess depressive-like behavior, the open field test (OFT) to assess locomotion, and the elevated plus maze to assess anxiety-like behavior. Results: The full-spectrum CBD extract at both doses, but not the CBD isolate, reversed the LPS-induced depressive-like behavior in the forced swim test. Moreover, the full-spectrum CBD extract at the higher dose but not the CBD isolate restored the subchronic LPS-induced hypolocomotion in the OFT. Repeated administration of both formulations elicited an anxiogenic-like trend in the elevated plus maze. Conclusion: Full-spectrum CBD products might have greater therapeutic efficacy in resolving inflammation-induced depressive and sickness behavior compared to a CBD-only isolate.

Mouse Exploratory Behaviour in the Open Field with and without NAT-1 EEG Device: Effects of MK801 and Scopolamine.

One aspect of reproducibility in preclinical research that is frequently overlooked is the physical condition in which physiological, pharmacological, or behavioural recordings are conducted. In this study, the physical conditions of mice were altered through the attachments of wireless electrophysiological recording devices (Neural Activity Tracker-1, NAT-1). NAT-1 devices are miniaturised multichannel devices with onboard memory for direct high-resolution recording of brain activity for >48 h. Such devices may limit the mobility of animals and affect their behavioural performance due to the added weight (total weight of approximately 3.4 g). The mice were additionally treated with saline (control), N-methyl-D-aspartate (NMDA) receptor antagonist MK801 (0.85 mg/kg), or the muscarinic acetylcholine receptor blocker scopolamine (0.65 mg/kg) to allow exploration of the effect of NAT-1 attachments in pharmacologically treated mice. We found only minimal differences in behavioural outcomes with NAT-1 attachments in standard parameters of locomotor activity widely reported for the open field test between the drug treatments. Hypoactivity was globally observed as a consistent outcome in the MK801-treated mice and hyperactivity in scopolamine groups regardless of NAT-1 attachments. These data collectively confirm the reproducibility for combined behavioural, pharmacological, and physiological endpoints even in the presence of lightweight wireless data loggers. The NAT-1 therefore constitutes a pertinent tool for investigating brain activity in, e.g., drug discovery and models of neuropsychiatric and/or neurodegenerative diseases with minimal effects on pharmacological and behavioural outcomes.

Evaluation of Antidepresant Activity and Phytochemical Screening of Plant Cordia Dichotoma.

INTRODUCTION: The traditional medicinal system of India, Ayurveda, has mentioned Cordia Dichotoma as a potential treatment for various ailments. In the current research, the extracts of Cordia Dichotoma was examined to evaluate their antidepressant potential. MATERIALS AND METHODS: Here, green leaves of Cordia Dichotoma were used to prepare chloroform, ethanol, and aqueous extracts (referred to as CdCe, CdEe, and CdAe respectively). The research focused on investigating the antidepressant effects of these extracts using behavioral models in experimental animals. Additionally, locomotor activity was assessed as part of the evaluation process. RESULTS: Immobility time was reduced with CdEe Cordia Dichotoma rFST & mTST when at 200 mg/kg and 400 mg/kg body weight. The CdAe showed reduction in immobility time in the repeated rFST) at 400 mg/kg, while in the mTST, significant effects were observed at 200 and 400 mg/kg. Regarding the chloroform extract, it only exhibited a significant reduction in immobility time in the modified Tail Suspension Test (mTST) at a low dose of 200 mg/kg. However, no noticeable change in motor dysfunction was observed with CCl4 and aqueous extracts at doses of 200 and 400 mg/kg. It is worth noting that the chloroform extract (CdCe) did lead to a significant decrease in locomotor activity at the same dosage level. Taken together, these findings suggest that extracts obtained from Cordia Dichotoma leaves may possess antidepressant properties.

Time association study on a sub-acute mouse model of Parkinson's disease.

Parkinson's disease (PD) is a severe neurodegenerative disease that disturbs human health. In the laboratory researches about PD, the mice model induced by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was widely used. However, there has been controversy about the model effectiveness to simulate PD symptoms and pathology, and the time-varying development of behavioral and pathological characteristic after MPTP treatment remains unclear. In order to solve these problems, we designed a series of experiments to evaluate this PD model at different time points. We constructed the subacute PD mouse model by intraperitoneal injection of MPTP for 5 consecutive days. The rotarod test, open field test and the immunohistochemical staining of tyrosine hydroxylase were conducted at -5, 1, 5, 7, 14, 21 and 28 days after the last injection of MPTP. The results showed that 5 days after the last MPTP administration, typical motor disorders with significant balance function damage in rotarod test began to appear and remained stable throughout the entire experiment. Simultaneously, we also observed the loss of tyrosine hydroxylase (TH) positive cells in the substantia nigra compacta and reduction of TH content in the striatum but this pathological change in the substantia nigra compacta reversed 21 days after injection. Besides, the spontaneous movement of mice in open field test remained unchanged by MPTP. This research indicated the time-dependence of MPTP neurotoxicity that impair the motor function and histological features and confirmed the symptom occurrence time after MPTP injection, which provides a reference for the future research about MPTP-induced PD.

The impact of estrous cycle on anxiety-like behaviour during unlearned fear tests in female rats and mice: A systematic review and meta-analysis.

Anxiety fluctuates across the human menstrual cycle, with symptoms worsening during phases of declining or low ovarian hormones. Similar findings have been observed across the rodent estrous cycle, however, the magnitude and robustness of these effects have not been meta-analytically quantified. We conducted a systematic review and meta-analysis of estrous cycle effects on anxiety-like behaviour (124 articles; k = 259 effect sizes). In both rats and mice, anxiety-like behaviour was higher during metestrus/diestrus (lower ovarian hormones) than proestrus (higher ovarian hormones) (g = 0.44 in rats, g = 0.43 in mice). There was large heterogeneity in the data, which was partially accounted for by strain, experimental task, and reproductive status. Nonetheless, the effect of estrous cycle on anxiety-like behaviour was highly robust, with the fail-safe N test revealing the effect would remain significant even if 21,388 additional studies yielded null results. These results suggest that estrous cycle should be accounted for in studies of anxiety in females. Doing so will facilitate knowledge about menstrual-cycle regulation of anxiety disorders in humans.

Effects of cannabidiol, with and without ∆9-tetrahydrocannabinol, on anxiety-like behavior following alcohol withdrawal in mice.

Introduction: Alcohol use disorder (AUD) is commonly associated with anxiety disorders and enhanced stress-sensitivity; symptoms that can worsen during withdrawal to perpetuate continued alcohol use. Alcohol increases neuroimmune activity in the brain. Our recent evidence indicates that alcohol directly modulates neuroimmune function in the central amygdala (CeA), a key brain region regulating anxiety and alcohol intake, to alter neurotransmitter signaling. We hypothesized that cannabinoids, such as cannabidiol (CBD) and ∆9-tetrahydrocannabinol (THC), which are thought to reduce neuroinflammation and anxiety, may have potential utility to alleviate alcohol withdrawal-induced stress-sensitivity and anxiety-like behaviors via modulation of CeA neuroimmune function. Methods: We tested the effects of CBD and CBD:THC (3:1 ratio) on anxiety-like behaviors and neuroimmune function in the CeA of mice undergoing acute (4-h) and short-term (24-h) withdrawal from chronic intermittent alcohol vapor exposure (CIE). We further examined the impact of CBD and CBD:THC on alcohol withdrawal behaviors in the presence of an additional stressor. Results: We found that CBD and 3:1 CBD:THC increased anxiety-like behaviors at 4-h withdrawal. At 24-h withdrawal, CBD alone reduced anxiety-like behaviors while CBD:THC had mixed effects, showing increased center time indicating reduced anxiety-like behaviors, but increased immobility time that may indicate increased anxiety-like behaviors. These mixed effects may be due to altered metabolism of CBD and THC during alcohol withdrawal. Immunohistochemical analysis showed decreased S100ß and Iba1 cell counts in the CeA at 4-h withdrawal, but not at 24-h withdrawal, with CBD and CBD:THC reversing alcohol withdrawal effects.. Discussion: These results suggest that the use of cannabinoids during alcohol withdrawal may lead to exacerbated anxiety depending on timing of use, which may be related to neuroimmune cell function in the CeA.

Behavioral neuroscience in zebrafish: unravelling the complexity of brain-behavior relationships.

This paper reviews the utility of zebrafish (Danio rerio) as a model system for exploring neurobehavioral phenomena in preclinical research, focusing on physiological processes, disorders, and neurotoxicity biomarkers. A comprehensive review of the current literature was conducted to summarize the various behavioral characteristics of zebrafish. The study examined the etiological agents used to induce neurotoxicity and the biomarkers involved, including Aß42, tau, MMP-13, MAO, NF-Кß, and GFAP. Additionally, the different zebrafish study models and their responses to neurobehavioral analysis were discussed. The review identified several key biomarkers of neurotoxicity in zebrafish, each impacting different aspects of neurogenesis, inflammation, and neurodegeneration. Aß42 was found to alter neuronal growth and stem cell function. Tau's interaction with tubulin affected microtubule stability and led to tauopathies under pathological conditions. MMP-13 was linked to oxidative assault and sensory neuron degeneration. MAO plays a role in neurotransmitter metabolism and neurotoxicity conversion. NF-Ðšß was involved in pro-inflammatory pathways, and GFAP was indicative of neuroinflammation and astroglial activation. Zebrafish provide a valuable model for neurobehavioral research, adhering to the "3Rs" philosophy. Their neurotoxicity biomarkers offer insights into the mechanisms of neurogenesis, inflammation, and neurodegeneration. This model system aids in evaluating physiological and pathological conditions, enhancing our understanding of neurobehavioral phenomena and potential therapeutic interventions.

TRPV1 and mast cell involvement in repeated variate stress-induced urinary bladder dysfunction in adult female mice.

The etiology of interstitial cystitis/bladder pain syndrome (IC/BPS) is unknown but likely multifactorial. IC/BPS symptoms can be exacerbated by psychological stress, but underlying mechanisms remain to be defined. Transient receptor potential vanilloid 1 (TRPV1) channels, expressed on nerve fibers, have been implicated in bladder dysfunction and colonic hypersensitivity with stress in rodents. Histamine/H1R activation of TRPV1+ nerves increases bladder afferent fiber sensitivity to distension. TRPV1 channels are also expressed on mast cells, previously implicated in contributing to IC/BPS etiology and symptoms. We have examined the contribution of TRPV1 and mast cells to bladder dysfunction after repeated variate stress (RVS). RVS increased (P ≤ 0.05) serum and fecal corticosterone expression and induced anxiety-like behavior in wild-type (WT) mice. Intravesical instillation of the selective TRPV1 antagonist capsazepine (CPZ) rescued RVS-induced bladder dysfunction in WT mice. Trpv1 knockout (KO) mice did not increase voiding frequency with RVS and did not exhibit increased serum corticosterone expression despite exhibiting anxiety-like behavior. Mast cell-deficient mice (B6.Cg-Kitw-sh) failed to demonstrate RVS-induced increased voiding frequency or serum corticosterone expression, whereas control (no stress) mast cell-deficient mice had similar functional bladder capacity to WT mice. TRPV1 protein expression was significantly increased in the rostral lumbar (L1-L2) spinal cord and dorsal root ganglia (DRG) in WT mice exposed to RVS, but no changes were observed in lumbosacral (L6-S1) spinal segments or DRG. These studies demonstrated TRPV1 and mast cell involvement in RVS-induced increased voiding frequency and suggest that TRPV1 and mast cells may be useful targets to mitigate stress-induced urinary bladder dysfunction.NEW & NOTEWORTHY Using pharmacological tools and transgenic mice in a repeated variate stress (RVS) model in female mice, we demonstrate that transient receptor potential vanilloid 1 (TRPV1) and mast cells contribute to the increased voiding frequency observed following RVS. TRPV1 and mast cells should continue to be considered as targets to improve bladder function in stress-induced bladder dysfunction.

Effective reduction in seizure severity and prevention of a fatty liver by a novel low ratio ketogenic diet composition in the rapid kindling rat model of epileptogenesis.

Drug-resistant epilepsy patients may benefit from non-pharmacological therapies, such as the ketogenic diet (KD). However, its high fat content poses compliance challenges and metabolic risks. To mitigate this, we developed a novel KD composition with less fat and additional nutrients (citrate, nicotinamide riboside, and omega-3 fatty acids) for ketone-independent neuroprotection. The efficacy, metabolic and neuropathological effects of the novel KD and a classic KD were compared to a control diet in the rapid kindling model of temporal lobe epilepsy. Both KD groups entered ketosis before kindling onset, with higher ketone levels in the classic KD group. Remarkably, rats on the novel KD had slower progression of behavioral seizures as compared to rats on a control diet, while this was not the case for rats on a classic KD. Both KDs reduced electrographic after-discharge duration, preserved neurons in the dorsal hippocampus, and normalized activity in open field tests. The novel KD, despite lower fat and ketone levels, demonstrated effective reduction of behavioral seizure severity while the classic KD did not, suggesting alternative mode(s) of action are involved. Additionally, the novel KD significantly mitigated liver triglyceride and plasma fatty acid levels compared to the classic KD, indicating a reduced risk of long-term liver steatosis. Our findings highlight the potential of the novel KD to enhance therapeutic efficacy and compliance in epilepsy patients.

Repeated Sulforaphane Treatment Reverses Depressive-like Behavior and Exerts Antioxidant Effects in the Olfactory Bulbectomy Model in Mice.

Growing evidence suggests that activators of nuclear factor erythroid-derived 2-like 2 (Nrf2), such as sulforaphane, may represent promising novel pharmacological targets for conditions related to oxidative stress, including depressive disorder. Therefore, we conducted a study to explore the behavioral and biochemical effects of repeated (14 days) sulforaphane (SFN) treatment in the olfactory bulbectomy (OB) animal model of depression. An open field test (OFT), splash test (ST), and spontaneous locomotor activity test (LA) were used to assess changes in depressive-like behavior and the potential antidepressant-like activity of SFN. The OB model induced hyperactivity in mice during the OFT and LA as well as a temporary loss of self-care and motivation in the ST. The repeated administration of SFN (10 mg/kg) effectively reversed these behavioral changes in OB mice across all tests. Additionally, a biochemical analysis revealed that SFN (10 mg/kg) increased the total antioxidant capacity in the frontal cortex and serum of the OB model. Furthermore, SFN (10 mg/kg) significantly enhanced superoxide dismutase activity in the serum of OB mice. Overall, the present study is the first to demonstrate the antidepressant-like effects of repeated SFN (10 mg/kg) treatment in the OB model and indicates that these benefits may be linked to improved oxidative status.

Nimodipine Protects Vascular and Cognitive Function in an Animal Model of Cerebral Small Vessel Disease.

BACKGROUND: Cerebral small vessel disease is a common cause of vascular cognitive impairment and dementia. There is an urgent need for preventative treatments for vascular cognitive impairment and dementia, and reducing vascular dysfunction may provide a therapeutic route. Here, we investigate whether the chronic administration of nimodipine, a central nervous system-selective dihydropyridine calcium channel blocking agent, protects vascular, metabolic, and cognitive function in an animal model of cerebral small vessel disease, the spontaneously hypertensive stroke-prone rat. METHODS: Male spontaneously hypertensive stroke-prone rats were randomly allocated to receive either a placebo (n=24) or nimodipine (n=24) diet between 3 and 6 months of age. Animals were examined daily for any neurological deficits, and vascular function was assessed in terms of neurovascular and neurometabolic coupling at 3 and 6 months of age, and cerebrovascular reactivity at 6 months of age. Cognitive function was evaluated using the novel object recognition test at 6 months of age. RESULTS: Six untreated control animals were terminated prematurely due to strokes, including one due to seizure, but no treated animals experienced strokes and so had a higher survival (P=0.0088). Vascular function was significantly impaired with disease progression, but nimodipine treatment partially preserved neurovascular coupling and neurometabolic coupling, indicated by larger (P<0.001) and more prompt responses (P<0.01), and less habituation upon repeated stimulation (P<0.01). Also, animals treated with nimodipine showed greater cerebrovascular reactivity, indicated by larger dilation of arterioles (P=0.015) and an increase in blood flow velocity (P=0.001). This protection of vascular and metabolic function achieved by nimodipine treatment was associated with better cognitive function (P<0.001) in the treated animals. CONCLUSIONS: Chronic treatment with nimodipine protects from strokes, and vascular and cognitive deficits in spontaneously hypertensive stroke-prone rat. Nimodipine may provide an effective preventive treatment for stroke and cognitive decline in cerebral small vessel disease.

Stress response to social isolation followed by exposure to a novel object in aged ewes born to undernourished mothers.

Fetal programming by subnutrition affects offspring's behaviour, metabolism, and sensitivity to stressors in sheep. The objective was to determine the stress response of ewes born to mothers nutritionally restricted during gestation to social isolation followed by exposure to a novel object. Twenty-six-year-old Corriedale ewes born to mothers who grazed high or low pasture allowances (HPA and LPA groups) from 23 days before conception until 122 days of gestation were used. Ewes were individually isolated in a novel place for 10 min, and 5 min after its beginning, an orange ball was dropped into the test pen. The ewes' behaviours were recorded during the test. Blood proteins, glucose and cortisol concentrations, heart and respiratory rates and rectal and surface temperatures were determined. The number of times looking at the ball tended to be greater in HPA ewes than LPA (6.7 ± 1.0 vs 4.7 ± 0.8, P = 0.08). The LPA ewes had greater serum albumin concentration than HPA ewes (3.2 ± 0.1 g/dL vs 3.0 ± 0.1 g/dL, P = 0.02), regardless of the applied stressors. Overall, the nutritional treatments applied to ewes during their intrauterine development did not modify the stress responses to social isolation followed by exposure to a novel object.

1H NMR-metabolomics studies on acute toxicity effect of lead in adult zebrafish (Danio rerio) model.

Zebrafish (Danio rerio) is ideal for studying the effects of toxins like lead or plumbum (Pb) which persist in the environment and harm body systems when absorbed. Increasing Pb concentration could result in a higher mortality rate and alteration of behavior and metabolism. The present study evaluates the acute toxicity effect of Pb on metabolome and behavior in adult zebrafish. The zebrafish were exposed to various Pb concentrations ranging from 0 to 30 mg/L for different periods (24, 48, and 72 h) before the fish samples were subjected to Nuclear Magnetic Resonance (NMR)-multivariate data analysis (MVDA) with additional support from behavioral assessment. The behavior of zebrafish was significantly altered after Pb inducement and the differential metabolites increased in low (5 mg/L) while decreased in high (10 mg/L) Pb concentrations. An ideal Pb induction could be achieved by 5 mg/L concentration in 24 h, which induced significant metabolite changes without irreversible damage. Continuing research on the effects of lead toxicity is crucial to develop effective prevention and treatment strategies.

Effects of oral administration of ondansetron, a 5-HT3 receptor antagonist, on anxiety-related behaviors and colonic hypercontractility in repeated stress-induced mice.

PURPOSE: Chronic psychological stress develops and exacerbates irritable bowel syndrome (IBS). 5-hydroxytryptamine (5-HT) via activation of intestinal 5-HT3 receptors involves impairment of intestinal functions. This study aimed to investigate the effects of ondansetron, a 5-HT3 receptor antagonist, on locomotor activity, anxiety-related behaviors, and colonic functions in repeated water avoidance stress. MATERIALS AND METHODS: Food intake and fecal pellet output (FPO) of sham stress (SS), water avoidance stress (WS), and water avoidance stress with oral administration of ondansetron (1 mg/kg BW) (WA) groups were monitored along the water avoidance stress protocol for 10 consecutive days. On day 11, locomotor activity and anxiety-related behaviors were determined using an open field test. Contractile properties of colonic tissues in response to KCl and a cumulative dose of carbachol (CCh) were determined using in vitro organ bath technique. RESULTS: FPO was significantly increased in the WS group after 7 days of water avoidance stress, which was reversed in WA group. WS group decreased unsupported rearing behavior compared to WS group, which was not altered in the WA group. The colon of the WS group had a higher tonic contraction in response to CCh than the SS and WA groups, which was reversed with ondansetron pre-incubation. CONCLUSIONS: Oral administration of ondansetron prevented increased FPO but did not affect anxiety-related behavior in repeated stress model. Colonic hypercontractility in the stressed mice was related to increased responses to cholinergic-induced contractions, which involved 5-HT3 receptors. Our findings suggest the modulatory roles of 5-HT3 receptors to mediate stress-induced colonic dysfunction.

Effect of high-intensity interval training on self-care and anxiety-like behaviors in naive rats.

Self-care behavior covers individual's health, life and well-being to maintain the necessary activities. The aim of this study is to examine the self-care and possible anxiolytic effects of high-intensity interval exercise (HIIT). Eight-week-old Wistar Albino male rats were divided into Control (n = 8), and Exercise (n = 8). Rat exercised for 38 min a day, 5 days a week, for 8 weeks The animals were then subjected to open field test and splash test, and the behaviors were video recorded. Student t test and Shapiro-Wilk test were used as statistical tests. In the exercise group, spray-induced grooming behavior increased significantly in terms of duration and frequency (p < 0.05), but no significant difference was observed in the latency of grooming (p > 0.05). In the open-field test, the total distance traveled, which is a locomotor activity parameter, did not change between the groups. Anxiolytic-like behaviors such as total rearing behavior, unsupported rearing, central time, and central region entries increased remarkably in the exercise group vs. control (p < 0.0001). Freezing as an anxiogenic behavior decreased in the exercise group positively (p < 0.0001). Intermittent high-intensity exercise improved and increased self-care behaviors. Further, the present study shows that HIIT has beneficial effects on different aspects of behaviors such as exploratory behaviors, increasing anxiolytic behaviors, and reducing anxiogenic behavior. The present study is a preclinical study that will pave the way for new studies.

Structural consistency of exploratory behaviour of sub-adult and adult spiny mice (Acomys cahirinus) in seven different tests.

The genus Acomys is of growing importance to many research fields. Previous research has shown that individuals differ when exploring new environments and that these behavioural strategies are consistent in time. In this study, we subjected 60 commensal Acomys cahirinus (37 males, 23 females) to a series of seven tests (free exploration, forced exploration under bright illumination, forced exploration under low illumination, hole board test, vertical activity test, elevated plus maze, and voluntary wheel running) to acquire independent behavioural traits and investigate whether and how personality develops in spiny mice. The full series of experiments was performed twice during ontogeny: once in the sub-adult stage (tested at 62-72 days of age) and once in the adult stage (102-112 days of age). We found that behaviour of the animals was repeatable both within (range of R values from 0.155 to 0.726) and across the two life-stages (0.238 to 0.563). While the structure of behaviour in adults was rather clear, it had not been fully crystalized in sub-adults, suggesting personality changes during maturation, even though some individual traits might be repeatable across ontogeny. Notably, the most consistent behavioural traits across the different tests were jumping and rearing, which are not commonly reported.

Involvement of the Na+, K+-ATPase α1 Isoform and Endogenous Cardiac Steroids in Depression- and Manic-like Behaviors.

Bipolar disorder (BD) is a severe and common chronic mental illness characterized by recurrent mood swings between depression and mania. The biological basis of the disease is poorly understood, and its treatment is unsatisfactory. Na+, K+-ATPase is a major plasma membrane transporter and signal transducer. The catalytic α subunit of this enzyme is the binding site for cardiac steroids. Three α isoforms of the Na+, K+-ATPase are present in the brain. Previous studies have supported the involvement of the Na+, K+-ATPase and endogenous cardiac steroids (ECS) in the etiology of BD. Decreased brain ECS has been found to elicit anti-manic and anti-depressive-like behaviors in mice and rats. However, the identity of the specific α isoform involved in these behavioral effects is unknown. Here, we demonstrated that decreasing ECS through intracerebroventricular (i.c.v.) administration of anti-ouabain antibodies (anti-Ou-Ab) decreased the activity of α1+/- mice in forced swimming tests but did not change the activity in wild type (wt) mice. This treatment also affected exploratory and anxiety behaviors in α1+/- but not wt mice, as measured in open field tests. The i.c.v. administration of anti-Ou-Ab decreased brain ECS and increased brain Na+, K+-ATPase activity in wt and α1+/- mice. The serum ECS was lower in α1+/- than wt mice. In addition, a study in human participants demonstrated that serum ECS significantly decreased after treatment. These results suggest that the Na+, K+-ATPase α1 isoform is involved in depressive- and manic-like behaviors and support that the Na+, K+-ATPase/ECS system participates in the etiology of BD.

Social Stress during the Estrus or Luteal Phase in Sheep.

In mammals, progesterone and estrogens affect the stress response. The study aimed to compare the physiological and behavioral responses to the social isolation of ewes during the estrus or luteal phase. Estrous and diestrous ewes (n = 10 and 8 respectively) were individually isolated in a novel place for 10 min. Ewes' behavior was recorded during the test. Cortisol, blood proteins and glucose concentrations, and the skin surface temperature were determined before and after the test. Cortisol increased immediately after the test ended (P = 0.02). Serum total protein (P = 0.02), globulin (P < 0.0001), and plasma glucose (P = 0.006) concentrations were greater in estrus than in the luteal phase. The abdominal skin surface temperature was greater during estrus than during the luteal phase (P = 0.02). Ewes in estrus spent more time standing up immobile than ewes in the luteal phase (P = 0.05). In conclusion, the physiological and behavioral responses changed according to the phase of the estrous cycle. These results highlight the need for future studies focusing on how reproductive status influences the stress response to different management practices in sheep.

Analysis of depression-like behavioral performances of mouse models of vitiligo / 中华皮肤科杂志

Objective:To observe and analyze depression-like behavioral performances of mouse models of vitiligo.Methods:Fifteen female C57BL/6 mice aged about 9 weeks were modeled for vitiligo. Whether the mouse models of vitiligo were successfully constructed or not was determined by macroscopy and full-thickness epidermal immunofluorescence staining of mouse tail tissues on day 23 after the start of the experiment; on day 8 (pre-modeling stage) and day 21 (early modeling stage), the elevated plus maze test and the open field test were used to evaluate the behavioral performances of the mice, including the number of entry into the open arms, percentages of time spent in the open arms, percentages of time spent in the central area and total distance traveled, aiming to assess whether depression-like behaviors were exhibited in the mouse models of vitiligo. To further clarify the degree of the impact of vitiligo modeling on the depression-like state in mice, 20 female C57BL/6 mice were equally divided into 2 groups: vitiligo modeling group and vitiligo modeling + chronic restraint stress group; the mice in the vitiligo modeling + chronic restraint stress group were subjected to chronic restraint stress on day 9, that is, these mice were placed in centrifuge tubes and restrained for about 6 hours every day for 28 consecutive days; on days 7, 22, 29 and 38 after the start of vitiligo modeling, the above-mentioned behavioral indicators were determined by the elevated plus maze test and open field test in the 2 groups. Repeated measurement data in a single group were compared before and after treatment by using paired t-test, and repeated measurement data at multiple time points were compared by using two-way repeated measures analysis of variance. Results:By macroscopy, the mice gradually developed well-defined white patches on the tail skin during vitiligo modeling, which were similar to the clinical manifestations of vitiligo patients; on day 23, full-thickness epidermal immunofluorescence staining of the mouse tail tissues was conducted and showed obvious infiltration of CD8 + T cells and a decrease in the number of Melan-A-positive epidermal melanocytes under a laser confocal microscope, which were consistent with typical pathological characteristics of vitiligo; based on the macroscopic results and immunofluorescence findings, a total of 12 mouse models of vitiligo were successfully constructed on day 23. The elevated plus maze test showed that the number of entry into the open arms and the percentages of time spent in the open arms were significantly lower in the 12 mouse models of vitiligo on day 21 (2.33 ± 1.78 times, 5.01% ± 5.27%, respectively) than in those on day 8 (10.75 ± 2.30 times, 29.20% ± 12.48%, t = 9.63, 6.36, respectively, both P < 0.001) ; the open field test showed that the percentages of time spent in the central area and total distance traveled were also significantly lower in the mouse models on day 21 (2.31% ± 1.53%, 2 518.31 ± 528.38 cm, respectively) than in those on day 8 (4.47% ± 2.65%, 3 533.45 ± 465.47 cm, t = 2.40, 5.47, P = 0.036, < 0.001, respectively). In the chronic restraint stress test, a total of 14 mouse models of vitiligo were successfully constructed on day 23, including 5 in the vitiligo modeling group and 9 in the vitiligo modeling + chronic restraint stress group. There were no significant differences in the number of entry into the open arms, percentages of time spent in the open arms, percentages of time spent in the central area, and total distance traveled between the vitiligo modeling group and the vitiligo modeling + chronic restraint stress group on days 7, 22, 29, and 38 ( F = 0.21, 0.20, 0.46, 2.35, P = 0.889, 0.893, 0.719, 0.134, respectively) ; moreover, all the above indicators significantly changed over time (all P < 0.001), except for the total distance traveled ( P = 0.422) . Conclusion:The mouse models of vitiligo developed depression-like behavior at the early modeling stage, and the degree of depression could not be further deepened by chronic restraint stress on the basis of vitiligo modeling.