Behavior In Rodents Research Articles

Analysis of behavioral flow resolves latent phenotypes.

The accurate detection and quantification of rodent behavior forms a cornerstone of basic biomedical research. Current data-driven approaches, which segment free exploratory behavior into clusters, suffer from low statistical power due to multiple testing, exhibit poor transferability across experiments and fail to exploit the rich behavioral profiles of individual animals. Here we introduce a pipeline to capture each animal's behavioral flow, yielding a single metric based on all observed transitions between clusters. By stabilizing these clusters through machine learning, we ensure data transferability, while dimensionality reduction techniques facilitate detailed analysis of individual animals. We provide a large dataset of 771 behavior recordings of freely moving mice-including stress exposures, pharmacological and brain circuit interventions-to identify hidden treatment effects, reveal subtle variations on the level of individual animals and detect brain processes underlying specific interventions. Our pipeline, compatible with popular clustering methods, substantially enhances statistical power and enables predictions of an animal's future behavior.

Beyond the information (not) given: Associative mechanisms versus representations of uncertainty in extinction in laboratory rats (Rattus norvegicus).

Associative learning models typically reflect statistical relationships between experienced events. Causal models can go beyond this information to specify the ways in which events are related. This meta-representational aspect of causal models allows them to reflect uncertainty about relationships between events: for example, if a light initially leads to sucrose but subsequently the light is experienced without sucrose, this might first support formation of a light-causes-sucrose model and subsequently lead to uncertainty over whether the model remained accurate. Prior studies of Pavlovian conditioning in rats manipulated sucrose-magazine access during extinction to produce uncertainty about reward presence or absence. Rats were sensitive to covering of the site of reward delivery, which was interpreted as evidence for a causal-model account reflecting uncertainty. However, associative accounts-based on the direct impact of the dipper mechanism used to deliver sucrose through secondary reinforcement or contextual renewal of responding-can also explain the results. In two new experiments, manipulation of the dipper mechanism through extinction and test phases resulted in behavior consistent with these associative accounts. However, demonstration of the importance of the sucrose dipper suggests that the reward delivery mechanism should be included in a causal model. Such a revised causal model also provides an account of the impact of manipulating the sucrose dipper. While these experiments do not conclusively decide between associative and causal models as explanations of rodent behavior, they do illustrate the value of incremental experimental study and the importance of methodological detail in addressing questions of comparative cognition. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Ethanolamine and Vinyl–Ether Moieties in Brain Phospholipids Modulate Behavior in Rats

Plasmalogens are brain-enriched phospholipids with a vinyl–ether bond at the sn-1 position between the glycerol backbone and the alkyl chain. Previous studies have suggested that plasmalogens modulate locomotor activity, anxiety-like behavior, and cognitive functions in rodents; however, the specific moieties contributing to behavioral regulation are unknown. In this study, we examined the behavioral modulation induced by specific phospholipid moieties. To confirm the permeability of phospholipids in injected liposomes, we measured the fluorescence intensity following intravenous injection of liposomes containing ATTO 740-labeled dioleoylphosphatidylethanolamine. Then, we compared the behavioral effects following injection of liposomes composed of egg phosphatidylcholine (PC) and 1-stearoyl-2-docosahexaenoyl-sn-glycero-3-phosphoethanolamine (PE 18:0/22:6), PC 18:0/22:6, 1-(1Z-octadecenyl)-2-docosahexaenoyl-sn-glycero-3-phosphoethanolamine (PE P-18:0/22:6), or PC P-18:0/22:6, into the tail vein of male rats. The time spent in the central region of the open field was significantly reduced after injection of PE 18:0/22:6, harboring an ester bond at sn-1 compared to controls. Furthermore, the discrimination ratio in the novel object recognition test was significantly higher in PC 18:0/22:6 compared to PE 18:0/22:6, suggesting that the substitution of ethanolamine with choline can enhance recognition memory. We demonstrate that the structures of the sn-1 bond and the hydrophilic moiety in the phospholipids can modulate exploratory behaviors and recognition memory in rodents.

Social contagion of pain and fear results in opposite social behaviors in rodents: meta- analysis of experimental studies.

The study aimed to explore the key factors influencing emotional valence in rodents, focusing on the critical elements that distinguish the contagion processes of fear and pain. Through a systematic review and meta-analysis, we examined behavioral outcomes of rodents exposed to painful or fearful catastrophes to see whether they are prosocial or antisocial through three-chamber test and dyadic social interaction paradigm. Fear contagion, particularly when witnessed, leads to social avoidance behavior, unaffected by sex difference but more pronounced with age. In contrast, pain contagion promotes social approach and caring/helping behaviors. The present study demonstrates that the emotional valence induced by pain contagion is quite different from fear contagion and this difference may result in different motivations and social behaviors, namely, social contagion of pain is likely to be more associated with prosocial behaviors, however, social contagion of fear is likely to be more associated with antisocial behaviors. PROSPERO (CRD42024566326).

Morphine-induced hyperalgesia impacts small extracellular vesicle miRNA composition and function.

Morphine and other synthetic opioids are widely prescribed to treat pain. Prolonged morphine exposure can paradoxically enhance pain sensitivity in humans and nociceptive behavior in rodents. To better understand the molecular mechanisms underlying opioid-induced hyperalgesia, we investigated changes in miRNA composition of small extracellular vesicles (sEVs) from the serum of mice after a morphine treatment paradigm that induces hyperalgesia. We observed significant differential expression of 18 miRNAs in sEVs from morphine-treated mice of both sexes compared to controls. Several of these miRNAs were bioinformatically predicted to regulate cyclic AMP response element binding protein (CREB), a well-characterized transcription factor implicated in pain and drug addiction. We confirmed the binding and repression of Creb mRNA by miR-155 and miR-10a. We tested if serum-derived sEVs from morphine-treated mice could elicit nociceptive behavior in naïve recipient mice. Intrathecal injection of 1 μg sEVs did not significantly impact basal mechanical and thermal threshold in naïve recipient mice. However, prophylactic 1 μg sEV administration in recipient mice resulted in faster resolution of complete Freund's adjuvant-induced mechanical and thermal inflammatory hypersensitivity. Other behaviors assayed following administration of these sEVs were not impacted including sEV conditioned place preference and locomotor sensitization. These results indicate that morphine regulation of serum sEV composition can contribute to analgesia and suggest a potential for sEVs to be a non-opioid therapeutic intervention strategy to treat pain.

Barbering in Laboratory Rodents: Problems and Prospects

Barbering is a behaviorally induced alopecia (hair and whisker biting) often observed in laboratory mice and rats. The role of this behavior is actively discussed, in particular, its relationship with stress, aggression, grooming and aberrant stereotypic behavior. Understanding the nature of barbering and its content in the state of laboratory animals is an important factor to consider in experimental work. Here, we discuss recent data on the neurobiology and genetics of barbering, as well as its role in the behavior and central nervous system of rodents.

REVEALS: an open-source multi-camera GUI for rodent behavior acquisition.

Deciphering the rich repertoire of mouse behavior is crucial for understanding the functions of both the healthy and diseased brain. However, the current landscape lacks effective, affordable, and accessible methods for acquiring such data, especially when employing multiple cameras simultaneously. We have developed REVEALS (Rodent Behavior Multi-Camera Laboratory Acquisition), a graphical user interface for acquiring rodent behavioral data via commonly used USB3 cameras. REVEALS allows for user-friendly control of recording from one or multiple cameras simultaneously while streamlining the data acquisition process, enabling researchers to collect and analyze large datasets efficiently. We release this software package as a stand-alone, open-source framework for researchers to use and modify according to their needs. We describe the details of the graphical user interface implementation, including the camera control software and the video recording functionality. We validate results demonstrating the graphical user interface's stability, reliability, and accuracy for capturing rodent behavior using DeepLabCut in various behavioral tasks. REVEALS can be incorporated into existing DeepLabCut, MoSeq, or other custom pipelines to analyze complex behavior. In summary, REVEALS offers an interface for collecting behavioral data from single or multiple perspectives, which, when combined with deep learning algorithms, enables the scientific community to identify and characterize complex behavioral phenotypes.

New insights into individual differences in response to chronic unpredictable mild stress (CUMS) in rats with respect to hippocampal BDNF and GSK3-β expression levels

Preclinical and clinical studies have shown a wide-range of individual differences in response to stressors or novel environments which can affect the susceptibility to develop abnormal behaviors and neuropsychiatric disorders. Both vulnerability and resiliency have been observed in animals and humans experiencing stressful events. Chronic unpredictable mild stress (CUMS) is a rodent depression model consisting of various stressors. This protocol leads to depressive- and anhedonic-like behaviors in rodents. The present study aimed to evaluate potential individual differences in response to CUMS in rats, with respect to the expression level of brain-derived neurotrophic factor (BDNF) and glycogen synthase kinases 3-beta (GSK3-β) (proteins involved in the modulation of mood, neuroplasticity, and cognition) in the hippocampus. CUMS was performed for four consecutive weeks. Depressive-like behavior, locomotor activity, anxiety-like behavior, and pain threshold were also evaluated using forced swim test (FST), open field test (OFT), and the hot plate (HP), respectively. Real-time PCR was used to evaluate BDNF and GSK3-β expression levels. The results showed that CUMS rats can be classified as two clusters: affected and non-affected (depressed and non-depressed). Affected rats showed depressive- and anxiety-like behaviors, decreased locomotor activity, and increased pain threshold. However, non-affected rats were similar to controls. In addition, there was a downregulation of BDNF and upregulation of GSK3-β in affected rats. Spearman correlation analysis also showed a relationship between BDNF and GSK3-β expression levels with individual differences. In conclusion, the present study showed that BDNF and GSK3-β may be involved in individual differences in CUMS rats.

Behavioral Assays for Comprehensive Evaluation of Cognitive and Neuropsychiatric Comorbidities of Traumatic Brain Injury and Chronic Neurological Disorders.

Neurological deficits, psychiatric disorders, and cognitive impairments often accompany stroke, brain injury, epilepsy, and many neurological disorders, which present intricate comorbidities that challenge recognition and management. There are many tools and paradigms for evaluating learning, memory, anxiety, and depression-like behaviors in lab animal models of brain disorders. However, there is a significant gap between clinical observations and experimental models, which limit understanding of the complex interplay between chronic brain conditions and their impact on cognitive dysfunction and psychiatric impairments. This article describes an overview of experimental rationale, methods, protocols, and strategies for evaluating sensorimotor, affective and cognitive-associated comorbid behaviors in epilepsy, traumatic brain injury (TBI), stroke, spinal cord injury (SCI), and many other neurological disorders. First, we delve into clinical evidence elucidating the profound impact of comorbidities, e.g., psychiatric disorders and cognitive deficits, in individuals with epilepsy. Then, we discuss diverse approaches to assess these comorbidities in experimental models of brain diseases. Finally, we explore the methodologies for assessing motor function, sensorimotor, behavior, and psychiatric health. We cover strategies and protocols enabling these assays, including implementing behavioral paradigms to assess learning and memory, anxiety, and depression-like behaviors in rodents in health and disease conditions. It is essential to consider a comprehensive battery of tests to investigate various behavioral deficits, considering environment, age, and sex differences relevant to the disease, such as TBI, SCI, epilepsy, stroke, and other complex neurological conditions. © 2024 The Author(s). Current Protocols published by Wiley Periodicals LLC.

AI-powered home cage system for real-time tracking and analysis of rodent behavior

AI-powered home cage system for real-time tracking and analysis of rodent behavior

Binge ethanol consumption can be attenuated by systemic administration of minocycline and is associated with enhanced neuroinflammation in the central amygdala

Alcohol use disorder (AUD) has a complicated pathophysiology. Binge ethanol intoxication may produce long-lasting changes throughout extended amygdala neurocircuitry including neuroinflammation, often leading to relapse. Therefore, understanding the role of binge drinking induced neuroinflammation on extended amygdala neurocircuitry is critically important for treatment. We sought to understand the role of neuroinflammation in a naturalized form of rodent binge ethanol drinking (Drinking in the Dark (DID)). In a 5-week DID paradigm, we demonstrate that acute intraperitoneal (IP) injection of the anti-inflammatory drug minocycline significantly reduced binge drinking repeatedly in male and female Cx3CR1-GFP and C57BL/6J mice. Importantly, IP administration transiently decreased intermittent access sucrose consumption, was not observed on the second IP injection, but did not significantly alter food or water consumption, suggesting that minocycline may produce initial acute aversive effects and may not alter long-term consumption of natural rewards. Examination of rodent behaviors post ethanol binge drinking reveals no lasting effects of minocycline treatment on locomotion or anxiety-like behavior. To assess neuroinflammation, we developed a novel analysis method using a Matlab image analysis script, which allows for non-biased skeletonization and evaluation of microglia morphology to determine a possible activation state in Cx3CR1-GFP knock-in mice after repeated DID. We observed significant morphological changes of microglia within the CeA, but no differences in the BLA. Taken together, this study demonstrates repeated binge ethanol consumption can produce significant levels of microglia morphology changes within the CeA, and that immunomodulatory therapies may be an intriguing pharmacological candidate for the treatment of AUD.

Animal Models of Autistic-like Behavior in Rodents: A Scoping Review and Call for a Comprehensive Scoring System

Appropriate animal models of human diseases are a cornerstone in the advancement of science and medicine. To create animal models of neuropsychiatric and neurobehavioral diseases such as autism spectrum disorder (ASD) necessitates the development of sufficient neurobehavioral measuring tools to translate human behavior to expected measurable behavioral features in animals. If possible, the severity of the symptoms should also be assessed. Indeed, at least in rodents, adequate neurobehavioral and neurological tests have been developed. Since ASD is characterized by a number of specific behavioral trends with significant severity, animal models of autistic-like behavior have to demonstrate the specific characteristic features, namely impaired social interactions, communication deficits, and restricted, repetitive behavioral patterns, with association to several additional impairments such as somatosensory, motor, and memory impairments. Thus, an appropriate model must show behavioral impairment of a minimal number of neurobehavioral characteristics using an adequate number of behavioral tests. The proper animal models enable the study of ASD-like-behavior from the etiologic, pathogenetic, and therapeutic aspects. From the etiologic aspects, models have been developed by the use of immunogenic substances like polyinosinic-polycytidylic acid (PolyIC), lipopolysaccharide (LPS), and propionic acid, or other well-documented immunogens or pathogens, like Mycobacterium tuberculosis. Another approach is the use of chemicals like valproic acid, polychlorinated biphenyls (PCBs), organophosphate pesticides like chlorpyrifos (CPF), and others. These substances were administered either prenatally, generally after the period of major organogenesis, or, especially in rodents, during early postnatal life. In addition, using modern genetic manipulation methods, genetic models have been created of almost all human genetic diseases that are manifested by autistic-like behavior (i.e., fragile X, Rett syndrome, SHANK gene mutation, neuroligin genes, and others). Ideally, we should not only evaluate the different behavioral modes affected by the ASD-like behavior, but also assess the severity of the behavioral deviations by an appropriate scoring system, as applied to humans. We therefore propose a scoring system for improved assessment of ASD-like behavior in animal models.

The significance of P.V. Simonov’s “need-information theory of emotions” in the development of modern neurobiology of behavior

The current paper shows the importance of the need-information theory of P.V. Simonov in the development of modern neurobiology of behavior. The essence of the theory and the underlying fundamental principles of the organization of behavior-environmental uncertainty, probabilistic predictions of reinforcement are briefly described. The first section reviews the current data on the important role of uncertain environments and probabilistic predictions in organization of behavior. Attention is drawn to the reinforcement prediction error and its significance in the organization of both social and individual behavior, as well as its role in the consolidation and reconsolidation of memory. The second section shows the influence of need-information theory on the development of the theoretical and experimental basis of individual differences, with a scheme presented for explaining such differences based on the fundamental principles of theory. The next section examines the role of need-information theory in understanding the mechanisms of decision-making under risk conditions, and the importance of the theory as a conceptual basis for the new developing field of science – neuroeconomics. And finally, the 4th section considers in detail the model of emotional resonance (contagion) proposed by P. Simonov, and modern views on social behavior, in general, and the altruistic and selfish behavior of rodents, in particular.

The conotoxin Contulakin-G reverses hypersensitivity observed in rodent models of cancer-induced bone pain without inducing tolerance or motor disturbance

Abstract As the incidence and survival rates of patients with cancer continues to grow, an increasing number of people are living with comorbidities, which often manifests as cancer-induced bone pain (CIBP). The majority of patients with CIBP report poor pain control from currently available analgesics. A conotoxin, Contulakin-G (CGX), has been demonstrated to be an antinociceptive agent in postsurgical and neuropathic pain states via a neurotensin receptor 2 (NTSR2)-mediated pathway. However, the efficacy and side effect profile of CGX have never been assessed in CIBP. Here, we evaluated CGX's antinociceptive potential in a rodent model of CIBP. We hypothesized that CGX engages the NTSR2 pathway, providing pain relief with minimal tolerance and motor side effects. Our results demonstrated that CGX intrathecal injection in mice with CIBP attenuated both spontaneous pain behaviors and evoked mechanical hypersensitivity, regardless of their sex. Furthermore, the antinociceptive effect of CGX was dependent upon expression of NTSR2 and the R-type voltage-gated calcium channel (Cav2.3); gene editing of these targets abolished CGX antinociception without affecting morphine antinociception. Examination of the side effect profile of CGX demonstrated that, unlike morphine, chronic intrathecal infusion maintained antinociception with reduced tolerance in rats with CIBP. Moreover, at antinociceptive doses, CGX had no impact on motor behavior in rodents with CIBP. Finally, RNAScope and immunoblotting analysis revealed expression of NTSR2 in both dorsal and ventral horns, while Cav2.3 was minimally expressed in the ventral horn, possibly explaining the sensory selectivity of CGX. Together, these findings support advancing CGX as a potential therapeutic for cancer pain.

Examining Brain Activity Responses during Rat Ultrasonic Vocalization Playback: Insights from a Novel fMRI Translational Paradigm.

Despite decades of preclinical investigation, there remains limited understanding of the etiology and biological underpinnings of anxiety disorders. Sensitivity to potential threat is characteristic of anxiety-like behavior in humans and rodents, but traditional rodent behavioral tasks aimed to assess threat responsiveness lack translational value, especially with regard to emotionally valenced stimuli. Therefore, development of novel preclinical approaches to serve as analogues to patient assessments is needed. In humans, the fearful face task is widely used to test responsiveness to socially communicated threat signals. In rats, ultrasonic vocalizations (USVs) are analogous social cues associated with positive or negative affective states that can elicit behavioral changes in the receiver. It is therefore likely that when rats hear aversive alarm call USVs (22 kHz), they evoke translatable changes in brain activity comparable with the fearful face task. We used functional magnetic resonance imaging in male and female rats to assess changes in BOLD activity induced by exposure to aversive 22 kHz alarm calls emitted in response to threatening stimuli, prosocial (55 kHz) USVs emitted in response to appetitive stimuli, or a computer-generated 22 kHz tone. Results show patterns of regional activation that are specific to each USV stimulus. Notably, limbic regions clinically relevant to psychiatric disorders (e.g., amygdala, bed nucleus of the stria terminalis) are preferentially activated by either aversive 22 kHz or appetitive 55 kHz USVs. These results support the use of USV playback as a promising translational tool to investigate affective processing under conditions of distal threat in preclinical rat models.

Advancing Post-Stroke Depression Research: Insights from Murine Models and Behavioral Analyses.

Post-stroke depression (PSD) represents a significant neuropsychiatric complication that affects between 39% and 52% of stroke survivors, leading to impaired recovery, decreased quality of life, and increased mortality. This comprehensive review synthesizes our current knowledge of PSD, encompassing its epidemiology, risk factors, underlying neurochemical mechanisms, and the existing tools for preclinical investigation, including animal models and behavioral analyses. Despite the high prevalence and severe impact of PSD, challenges persist in accurately modeling its complex symptomatology in preclinical settings, underscoring the need for robust and valid animal models to better understand and treat PSD. This review also highlights the multidimensional nature of PSD, where both biological and psychosocial factors interplay to influence its onset and course. Further, we examine the efficacy and limitations of the current animal models in mimicking the human PSD condition, along with behavioral tests used to evaluate depressive-like behaviors in rodents. This review also sets a new precedent by integrating the latest findings across multidisciplinary studies, thereby offering a unique and comprehensive perspective of existing knowledge. Finally, the development of more sophisticated models that closely replicate the clinical features of PSD is crucial in order to advance translational research and facilitate the discovery of future effective therapies.

Neonatal paw pricking alters adolescent behavior in a sex-dependent manner and sucrose partially remediates the effects

Neonatal exposure to noxious stimuli such as repeated heel lances can cause behavior changes. In the NICU sucrose given prior to procedures attenuates the immediate behavioral response to noxious stimuli but may not ameliorate the long-term consequences, and treatment with 24 % sucrose can brain structure and behavior in adult rodents. We used a rat model to determine whether paw pricks during the neonatal period alter social interaction and/or paw withdrawal thresholds (PWT) in adolescence, and if 7 % sucrose mitigates these effects. One male and one female pup per litter was assigned to each of six experimental groups (no paw prick (control), 1 paw prick (1PP), or 2PP, ± sucrose). Hind paws were pricked once or twice each day between postnatal day (P)3 and P10. Social behavior and PWT were tested in adolescence using the modified social interaction test and von Frey filaments, respectively. Social behavior was altered in the 2PP group; total time interacting was lower in 2PP rats, primarily due to less time sniffing a play partner. Sucrose did not mitigate effects of paw prick but trended to alter social behaviors in males; it decreased time in contact but increased social motivation (movement toward a play partner). PWTs were higher in 2PP animals, this was not altered by sucrose. Thus, rat pups exposed to paw pricks in the neonatal period have some altered behaviors in adolescence. The nature of the behavioral changes is sex-dependent, but sucrose did not mitigate these changes.

Влияние содержания действующего вещества в родентицидном средстве на эффективность дератизационных обработок

House mice, gray rats and other mouse-like rodents pose a threat to human health and cause significant damage to its activities. Despite significant advances in deratization practice, rodent control currently remains a significant problem, since these biological species have a unique genetic ability to rapidly recover and increase their numbers. The rodent control program should be based on data on the ecology, behavior and preferences of rodents, their sensitivity to active substances, the specific situation of a certain object and territory. Each species has its own characteristics. It is necessary to take into account species preferences when developing the composition and form of application of rodenticidal baits. It is important to ensure the achievement of target values in the consumption of the product by rodents, its effectiveness, safety in relation to non-target species and safety during its placement and use. It is necessary to take into account what concentration of the active substance (DV) for rodents will be fatal, how much rodenticidal bait will be required for their death and for how long this amount of bait will be eaten by them. The effectiveness of the conducted deratization treatments is directly influenced by the content of the active substance in the applied rodenticidal agent. The analysis of the effectiveness of rodenticidal baits with different contents of the active substance bromadiolone in relation to house mice and gray rats showed that with a decrease in the concentration of DV in the bait, the period from the beginning of its eating to the onset of irreversible changes in the body of rodents leading to their death occurs. The placement of baits during deratization treatments should take place taking into account the species characteristics of rodents. In terms of body weight, the amount of absorbed DV by the body of a house mouse in comparison with a gray rat when eating rodenticidal bait is significantly higher, which is observed in the average daily and total intake. But in quantitative terms, gray rats consume significantly more bait. For the death of a house mouse, an average of about 8 g of bait is required with a bromadiolone content of 0.005?%, and the minimum amount was 3.2 g. For a gray rat, the average amount of bait was 32.4 g, and the minimum ~ 10 g. Taking into account these data, the amount of bait placed at the facility will vary from the number of rodents and the feedability of baits. A lower content of DV in baits contributes to an increase in their consumption during deratization treatments. With a high number of rodents, the amount of bait placed must be multiplied. Keywords: synanthropic rodents, gray rat, house mouse, deratization measures, anticoagulants, bromadiolone.

Exploring the Antidepressant-like Effects of Wogonin: Analysis of Behavioural, Neurochemical, and Biochemical Parameters

Background: Wogonin, a bioactive compound isolated from S. barbata D. Don, has been identified in the literature as a potential inhibitor of monoamine oxidase (MAO), a key enzyme involved in the degradation of neurotransmitters associated with mood regulation. This study aims to investigate the antidepressant-like activity of wogonin in vivo, utilizing a preclinical model. The rationale for selecting wogonin stems from its documented MAO inhibitory properties, suggesting a potential role in modulating neurotransmitter levels implicated in depressive disorder. Method: The study employs a multifaceted approach, incorporating behavioural, neurochemical, and biochemical assessments. The Chronic Unpredictable Mild Stress model is utilized to induce depression-like behavior in rodents for 21 days. Two doses of wogonin (20 and 40 mg/kg per orally) and standard (fluoxetine, 20 mg/kg, and imipramine, 15 mg/kg) were administered to albino mice. Behavioural paradigms, including the Tail Suspension Test, Forced Swim Test, and Open Field Test, are employed to assess the impact of wogonin on depressive-like symptoms on the 21st day. Neurochemical analyses focus on alterations in 5-HT, NE, and DA levels within relevant brain regions, and MAO activity is quantified to ascertain wogonin's potential as an MAO inhibitor on the 22nd day. Biochemical assessments emphasize wogonin's antioxidant properties and its ability to mitigate oxidative stress, a significant factor in depression pathophysiology. Plasma nitrite levels are measured to elucidate wogonin's impact on nitric oxide signalling. Plasma corticosteroid levels are also quantified to delineate wogonin's effect on the hypothalamicpituitary- adrenal (HPA) axis, a central regulator of stress response. Results: Wogonin demonstrates significant antidepressant effects in a dose-dependent manner in the behavioural assessments, showing a marked reduction in depressive-like behaviours across all paradigms. Neurochemical analyses revealed a significant (p ≤ 0.05) restoration of monoamine neurotransmitter levels in the relevant brain regions as compared to CUMS-induced stress group. Additionally, wogonin exhibits a potent (p ≤ 0.05) inhibitory effect on MAO activity. Biochemical assessments demonstrate a significant (p ≤ 0.05) increase in antioxidant capacity and a reduction in oxidative stress markers. Plasma nitrite levels indicate an enhancement of nitric oxide signalling. Corticosteroid levels showed a modulation of the HPA axis, suggesting a regulatory effect on stress response. Conclusion: This comprehensive study establishes wogonin as a promising MAO inhibitor with notable antidepressant potential. The findings provide crucial insights into its mechanisms of action, indicating a multifaceted approach to alleviating depression. Wogonin's demonstrated efficacy across behavioural, neurochemical, and biochemical parameters presents a strong foundation for further research and development of wogonin-based antidepressant interventions.

A Systematic Review and Meta-Analysis of Anxiety- and Depressive-Like Behaviors in Rodent Models of Neuropathic Pain

BackgroundEpidemiological studies have frequently shown the concurrence of chronic pain with symptoms of anxiety and depression, particularly in women. Animal models are useful to understand the complex mechanisms underlying comorbidities, but the wide range of methods employed and the wealth of evidence sometimes impedes effective translation and reproducibility. In this systematic review and meta-analysis, we aimed to synthesize the evidence regarding the influence of variables such as sex and species on anxiety- and depressive-like behaviors in rodent models of neuropathic pain. MethodsFollowing PROSPERO registration, we searched EMBASE, Scopus, and the Web of Science from their inception to November 24, 2023, identifying 126 studies that met the inclusion criteria. The Hedges’ g value for each experiment and study was calculated, and further subgroup and meta-regression analyses were performed. ResultsNeuropathic pain significantly reduced the time that rats and mice spent in the open arms of the elevated plus and zero mazes (g = −1.14), time spent in the center of the open field (g = −1.12), sucrose consumption in the sucrose preference test (g = −1.43), and grooming time in the splash test (g = −1.37) while increasing latency to feed in the novelty-suppressed feeding test (g = 1.59) and immobility in the forced swimming (g = 1.85) and tail suspension (g = 1.91) tests. Sex differences were observed, with weaker effects in female than in male rodents for several behavioral paradigms, and funnel plots identified positive publication bias in the literature. ConclusionsThis meta-analysis emphasizes the effect of neuropathic pain on anxiety- and depressive-like behaviors in rodents, highlighting the importance of investigating sex differences in future experimental studies.