Open-field exploration immediately before the retention test impairs retrieval and spaced fear extinction of contextual fear memory.

According to the behavioral tagging theory, various stages of fear memory, such as contextual fear conditioning, memory retrieval, and fear extinction, can be facilitated by the exploration of a novel open field (OF). A critical time window of efficacy exists for this process. Novel exploration closely adjacent to weak learning may interfere with the setting of the learning tag, leading to a negative effect. In this mouse study, we consistently showed that exposure to a novel or familiar OF immediately prior to the retention test impaired the retrieval of long-term contextual fear memory. However, OF exposure had no effect on the retrieval of recent or remote cued fear memory or short-term contextual fear memory or the reconsolidation of contextual fear memory. In addition, OF exposure impaired spaced but not massed extinction of contextual fear memory. These results suggest that interfering stimulus may result in the transient forgetting of fear memory; however, temporary loss of fear may lead to retention failure of fear extinction. The results of this study are an important complement to the behavioral tagging theory and may provide new guidance for the treatment of post-traumatic stress disorder.

A convolutional neural network model detecting lasting behavioral changes in mice with kanamycin-induced unilateral inner ear dysfunction.

In acute aminoglycoside ototoxicity of the unilateral inner ear, physical abnormalities, such as nystagmus and postural alteration, are relieved within a few days by neural compensation. To examine exploratory behavior over an extended period, behaviors of freely moving mice after unilateral kanamycin injection into the inner ear were recorded in a home cage environment. The tail was excluded from deep learning-mediated object detection because of its delayed movement relative to the body. All detection results were confirmed using a convolutional neural network classification model. In kanamycin-injected mice, the total distance moved in 15 min increased on postoperative day 3. Furthermore, injured mice turned more frequently toward the healthy side up to 17 days after the surgery. This tendency resulted in increased clockwise movements in home cage recordings. Moreover, tail suspension and twisting toward the healthy side induced a physical sign for up to 14 days after the injury; the mice rapidly rotated with dorsal bending. Our analysis strategy employing deep learning helps to evaluate neuronal compensatory processes for an extended period and is useful for assessing the efficacy of therapeutic interventions.

Ketamine modulates the exploratory dynamics and homebase-related behaviors of adult zebrafish.

Anxiety can be a protective emotion when animals face aversive conditions, but is commonly associated with various neuropsychiatric disorders when pathologically exacerbated. Drug repurposing has emerged as a valuable strategy based on utilizing the existing pharmaceuticals for new therapeutic purposes. Ketamine, traditionally used as an anesthetic, acts as a non-competitive antagonist of the glutamate N-methyl-d-aspartate (NMDA) receptor, and shows potential anxiolytic and antidepressant effects at subanesthetic doses. However, the influence of ketamine on multiple behavioral domains in vertebrates is not completely understood. Here, we evaluated the potential modulatory effect of ketamine on the spatio-temporal exploratory dynamics and homebase-related behaviors in adult zebrafish using the open field test (OFT). Animals were exposed to subanesthetic concentrations of ketamine (0, 2, 20, and 40 mg/L) for 20 min and their locomotion-, exploration- and homebase-related behaviors were assessed in a single 30-min trial. Our data revealed that acute ketamine (20 and 40 mg/L) induced hyperlocomotion, as verified by the increased total distance traveled. All concentrations tested elicited circling behavior, a stereotyped-like response which gradually reduced across the periods of test. We also observed modulatory effects of ketamine on the spatio-temporal exploratory pattern, in which the reduced thigmotaxis and homebase activity, associated with the increased average length of trips, suggest anxiolytic-like effects. Collectively, our findings support the modulatory effects of ketamine on the spatio-temporal exploratory activity, and corroborate the utility of homebase-related measurements to evaluate the behavioral dynamics in zebrafish models.

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.

Developmental Changes in Locomotion and Sensorimotor Reflexes Following Spinal Cord Transection.

The developmental trajectory of weight-bearing locomotion and sensorimotor reflexes following a spinal cord injury, as well as the mechanisms for plasticity, remain unclear. In rats, the second postnatal week is a critical period for the development and recovery of spinal sensorimotor function. The purpose of the present study was to characterize developmental changes during this time frame to provide a basis for potential interventions and future research. Rats underwent a complete low-thoracic (T8-T10) spinal cord transection surgery, or sham procedure, on postnatal day (P)1. Spontaneous locomotion and sensorimotor reflexes (surface righting, hindlimb placing, and crossed-extensor reflex) were tested on P7, P14, or P21. Results show that spinal-transected and sham rats exhibited the same amount of spontaneous locomotion, but the degree of relative weight bearing on the hindlimbs was different between groups and changed over time. Reflex findings showed that throughout the neonatal period, the isolated lumbar spinal cord can respond to sensory input and execute coordinated motor output following spinal cord transection. These insights contribute to understanding the developmental trajectory of spinal cord function after injury and provide a foundation for interventions to enhance recovery outcomes.

Machine learning reveals prominent spontaneous behavioral changes and treatment efficacy in humanized and transgenic Alzheimer's disease models.

Computer-vision and machine-learning (ML) approaches are being developed to provide scalable, unbiased, and sensitive methods to assess mouse behavior. Here, we used the ML-based variational animal motion embedding (VAME) segmentation platform to assess spontaneous behavior in humanized App knockin and transgenic APP models of Alzheimer's disease (AD) and to test the role of AD-related neuroinflammation in these behavioral manifestations. We found marked alterations in spontaneous behavior in AppNL-G-F and 5xFAD mice, including age-dependent changes in motif utilization, disorganized behavioral sequences, increased transitions, and randomness. Notably, blocking fibrinogen-microglia interactions in 5xFAD-Fggγ390-396A mice largely prevented spontaneous behavioral alterations, indicating a key role for neuroinflammation. Thus, AD-related spontaneous behavioral alterations are prominent in knockin and transgenic models and sensitive to therapeutic interventions. VAME outcomes had higher specificity and sensitivity than conventional behavioral outcomes. We conclude that spontaneous behavior effectively captures age- and sex-dependent disease manifestations and treatment efficacy in AD models.

Adolescent development of anxiety-related behavior and shifts in behavioral responsiveness to estradiol in female mice.

Early pubertal onset during adolescence is consistently linked with increased risk of anxiety and depression in girls. Although estradiol tends to have anxiolytic effects in adulthood, whether sensitivity to estradiol's anxiolytic actions increases during adolescence is not clear. Using a rodent model, the current study tested the hypothesis that a shift in sensitivity to the anxiolytic effects of estradiol occurs during adolescence. To test this hypothesis, prepubertal and adult C57BL/6 female mice were ovariectomized, implanted with vehicle- or estradiol-filled silastic capsules, and behavioral tested one week later in the open field and elevated zero maze. Our hypothesis predicted that estradiol would decrease anxiety-related behavior to a greater extent in adults than in adolescent females, however, our results did not support this hypothesis. In the open field, estradiol implants significantly decreased anxiety-like behavior in adolescent females (relative to vehicle) and had little to no effect on the behavior of adults. These data suggest that adolescence is associated with a downward shift in sensitivity to the anxiolytic effects of estradiol on behavior in the open field. In contrast, although estradiol treatment did not influence anxiety-like responses in the elevated zero maze in early adolescent or adult females, adolescent females displayed significantly higher levels of anxiety-like behavior than adults. These findings demonstrate that substantial changes in anxiety-related behavior occur during adolescence, including a context-dependent shift in behavioral responsiveness to estradiol.

Parkinson's LRRK2-G2019S risk gene mutation drives sex-specific behavioral and cellular adaptations to chronic variable stress.

Anxiety is a psychiatric non-motor symptom of Parkinson's that can appear in the prodromal period, prior to significant loss of midbrain dopamine neurons and motor symptoms. Parkinson's-related anxiety affects females more than males, despite the greater prevalence of Parkinson's in males. How stress, anxiety and Parkinson's are related and the basis for a sex-specific impact of stress in Parkinson's are not clear. We addressed this using young adult male and female mice carrying a G2019S knockin mutation of leucine-rich repeat kinase 2 (Lrrk2 G2019S) and Lrrk2 WT control mice. In humans, LRRK2 G2019S significantly elevates the risk of late-onset Parkinson's. To assess within-sex differences between Lrrk2 G2019S and control mice in stress-induced anxiety-like behaviors in young adulthood, we used a within-subject design whereby Lrrk2 G2019S and Lrrk2 WT control mice underwent tests of anxiety-like behaviors before (baseline) and following a 28 day (d) variable stress paradigm. There were no differences in behavioral measures between genotypes in males or females at baseline, indicating that the mutation alone does not produce anxiety-like responses. Following chronic stress, male Lrrk2 G2019S mice were affected similarly to male wildtypes except for novelty-suppressed feeding, where stress had no impact on Lrrk2 G2019S mice while significantly increasing latency to feed in Lrrk2 WT control mice. Female Lrrk2 G2019S mice were impacted by chronic stress similarly to wildtype females across all behavioral measures. Subsequent post-stress analyses compared cFos immunolabeling-based cellular activity patterns across several stress-relevant brain regions. The density of cFos-activated neurons across brain regions in both male and female Lrrk2 G2019S mice was generally lower compared to stressed Lrrk2 WT mice, except for the nucleus accumbens of male Lrrk2 G2019S mice, where cFos-labeled cell density was significantly higher than all other groups. Together, these data suggest that the Lrrk2 G2019S mutation differentially impacts anxiety-like behavioral responses to chronic stress in males and females that may reflect sex-specific adaptations observed in circuit activation patterns in some, but not all stress-related brain regions.

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.

Sucrose binge-eating and increased anxiety-like behavior in Sprague-Dawley rats exposed to repeated LPS administration followed by chronic mild unpredictable stress.

Exposure to persistent mild stress is a frequently encountered chronic challenge in a rapidly evolving society. Depending on various factors including sex, the response to stressors varies and is closely linked to the phenomenon of resilience. Depression and anxiety can be considered maladaptive responses to such stress. In this rat study, we investigated the sex-dependent effects of low-grade systemic inflammation during 1 week in combination with chronic unpredictable mild stress during the following 4 weeks on anxiety-like behavior and episodic feeding behavior. Increased anxiety-like behavior and increased sucrose intake were identified in stressed compared to control animals regardless of sex. Interestingly, two nearly equally distributed subpopulations were found in the stressed groups within each sex at the end of the 5-week protocol of combined stress exposure: the resistant and the susceptible, which were characterized by unchanged and increased sucrose intake, respectively. This difference in susceptibility to protracted combined mild stress and ensuing response to a sucrose eating binge demonstrates the complexity of the underlying regulatory mechanisms associated with emotional hyperreactivity. This model carries the potential for further investigation of the molecular basis of resilience and susceptibility to combined stressors and for testing treatments with potential preventive or therapeutic effects.

Behavioral mirroring in Wistar rats investigated through temporal pattern analysis.

The study of social interactions lies at the core of several disciplines such as psychiatry, psychology and ethology, just to name a few. In this context, understanding the temporal patterns underlying interactive behaviors is of crucial importance. Here, we employed T-pattern detection and analysis to study social interactions in ten pairs of Wistar rats tested in an Open-Field environment. We found four different categories of interactive behaviors. One of them was of particular interest to us because it consisted of behavioral events that, taken individually, should not underlie an interaction of any kind; however, they were included in T-patterns, which is suggestive of a dyadic temporal coordination in the behavioral expression of two individuals. Within this category, we described for the first time a new subcategory of apparent interaction patterns characterized by events that one of the two rats repeats only if previously produced by the partner (i.e., behavioral mirroring). These findings are discussed in functional terms for rodents and in light of our current understanding of social interactions in humans.

Impairments of social interaction in a valproic acid model in mice.

Background: A rodent autism spectrum disorder (ASD) model based on prenatal exposure to valproic acid (VPA) is widely recognized as a prominent model. Social behavior in rodent ASD models has primarily been evaluated through a three-chamber approach test. However, in this study, we focused on social attention in the VPA model of ASD. Methods: In male C57BL/6 J mice, attentional behaviors toward conspecifics were examined through reaching tasks around 9-11 weeks of age. On embryonic day 12.5, pregnant mice underwent a subcutaneous injection of 600 mg/kg VPA sodium salt dissolved in 0.9% saline solution (VPA group) or saline solution alone (Sal group) into their neck fat. Thirty-six mice-nine each in the VPA and saline groups, and 18 partners-underwent training in reaching behavior. Subsequently, we examined whether the VPA or Sal group demonstrated focused attention toward their partners during reaching tasks. A two-way analysis of variance (ANOVA) (condition [VPA/Sal] × situation [face-to-face (attention)/not paying attention (not attention)]) was conducted on the average success rate of the situation. Additionally, we measured the duration of sniffing behavior between pairs of mice in an open field twice in total at 4 and 8 weeks of age before reaching task. The pairs were constructed by pairing a VPA or Sal group mouse with its partner, with the objective of facilitating initial encounters between the mice. A one-way ANOVA was conducted on the average duration of sniffing behavior data from 4 weeks and a second one-way ANOVA on data from 8 weeks. Results: The analysis revealed a significant interaction between condition and situation in the reaching task [F (1, 28) = 6.75, p = 0.015, ηp 2 = 0.19]. The simple main effect test exhibited that the "not paying attention" rate was significantly higher than that of the "face-to-face" in the VPA group (p < 0.01). The results revealed a not significant difference in the average duration of sniffing behavior at 4 weeks [F (3, 32) = 2.71, p = 0.06, n.s., ηp 2 = 0.20], but significant difference at 8 weeks [F (3, 32) = 4.12, p < 0.05, ηp 2 = 0.28]. Multiple comparisons using the Bonferroni method revealed significant differences in the sniffing duration at 8 weeks between from the partner toward the VPA mouse and from the partner toward the Sal mouse (p < 0.05). Conclusion: The VPA rodent model of ASD exhibited differences in social attention compared to the saline group. By focusing on social attention and exploring various ASD models, insights can be gained from the neural mechanisms underlying gaze abnormalities during social interaction in individuals with ASD.

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.

Assessing the Fates of Water and Nitrogen on an Open-Field Intensive Vegetable System under an Expert-N System with EU-Rotate_N Model in North China Plain.

Nitrate leaching, greenhouse gas emissions, and water loss are caused by conventional water and fertilizer management in vegetable fields. The Expert-N system is a useful tool for recommending the optimal nitrogen (N) fertilizer for vegetable cultivation. To clarify the fates of water and N in vegetable fields, an open-field vegetable cultivation experiment was conducted in Dongbeiwang, Beijing. This experiment tested two irrigation treatments (W1: conventional and W2: optimal) and three fertilizer treatments (N1: conventional, N2: optimal N rate by Expert-N system, and N3: 80% optimal N rate) on cauliflower (Brassica oleracea L.), amaranth (Amaranthus tricolor L.), and spinach (Spinacia oleracea L.). The EU-Rotate_N model was used to simulate the fates of water and N in the soil. The results indicated that the yields of amaranth and spinach showed no significant differences among all the treatments in 2000 and 2001. However, cauliflower yield under the W1N2 and W1N3 treatments obviously reduced in 2001. Compared with the W1 treatment, W2 reduced irrigation amount by 27.9-29.8%, water drainage by over 76%, increased water use efficiency by 5-17%, and irrigation water use efficiency by 29-45%. Nitrate leaching was one of the main pathways in this study, accounting for 8.4% of the total N input; compared to N1, the input of fertilizer N under the N2 and N3 treatments decreased by over 66.5%, consequently reducing gaseous N by 48-72% and increasing nitrogen use efficiency (NUE) by 17-37%. Additionally, compared with the W1 treatments, gaseous N loss under the W2 treatments was reduced by 18-26% and annual average NUEs increased by 22-29%. The highest annual average NUEs were under W2N3 (169.6 kg kg-1) in 2000 and W2N2 (188.0 kg kg-1) in 2001, respectively. We found that optimizing fertilizer management allowed subsequent crops to utilize residual N in the soil. Therefore, we suggest that the W2N3 management should be recommended to farmers to reduce water and N loss in vegetable production systems.

Social deficits mirror delayed cerebrovascular dysfunction after traumatic brain injury.

Traumatic brain injury (TBI) survivors face debilitating long-term psychosocial consequences, including social isolation and depression. TBI modifies neurovascular physiology and behavior but the chronic physiological implications of altered brain perfusion on social interactions are unknown. Adult C57/BL6 male mice received a moderate cortical TBI, and social behaviors were assessed at baseline, 3-, 7-, 14-, 30-, and 60-days post injury (dpi). Magnetic resonance imaging (MRI, 9.4T) using dynamic susceptibility contrast perfusion weighted MRI were acquired. At 60dpi mice underwent histological angioarchitectural mapping. Analysis utilized standardized protocols followed by cross-correlation metrics. Social behavior deficits at 60dpi emerged as reduced interactions with a familiar cage-mate (partner) that mirrored significant reductions in cerebral blood flow (CBF) at 60dpi. CBF perturbations were dynamic temporally and across brain regions including regions known to regulate social behavior such as hippocampus, hypothalamus, and rhinal cortex. Social isolation in TBI-mice emerged with a significant decline in preference to spend time with a cage mate. Cortical vascular density was also reduced corroborating the decline in brain perfusion and social interactions. Thus, the late emergence of social interaction deficits mirrored the reduced vascular density and CBF in regions known to be involved in social behaviors. Vascular morphology and function improved prior to the late decrements in social function and our correlations strongly implicate a linkage between vascular density, cerebral perfusion, and social interactions. Our study provides a clinically relevant timeline of alterations in social deficits alongside functional vascular recovery that can guide future therapeutics.

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.

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.

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.

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.

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.