Explore the vast range of titles available.

Despite numerous studies on the neurobiology of depression, the etiological and pathophysiological mechanisms of this disorder remain poorly understood. A large number of animal models and tests to evaluate depressive-like behavior have been developed. Chronic unpredictable mild stress (CUMS) is the most common and frequently used model of depression, and the sucrose preference test (SPT) is one of the most common tests for assessing anhedonia. However, not all laboratories can reproduce the main effects of CUMS, especially when this refers to a decrease in sucrose preference. It is also unknown how the state of anhedonia, assessed by the SPT, relates to the state of anhedonia in patients with depression. We analyzed the literature available in the PubMed database using keywords relevant to the topic of this narrative review. We hypothesize that the poor reproducibility of the CUMS model may be due to differences in sucrose consumption, which may be influenced by such factors as differences in sucrose preference concentration threshold, water and food deprivation, and differences in animals’ susceptibility to stress. We also believe that comparisons between animal and human states of anhedonia should be made with caution because there are many inconsistencies between the two, including in assessment methods. We also tried to offer some recommendations that should improve the reproducibility of the CUMS model and provide a framework for future research.

Depression affects women nearly twice as frequently as men. In contrast, rodent models of depression have shown inconsistent results regarding sex bias, often reporting more depression-like symptoms in males. This sex discrepancy in rodents modeling depression may rely on differences in the baseline activity of males and females in depression-related behavioral tests. We previously showed that the baseline despair and anhedonia behaviors, major endophenotypes of depression, are not sex biased in young adolescent mice of C57BL/6N, DBA/2 and FVB/N inbred wild-type strains. Since the prevalence of depression in women peaks in their reproductive years, we here investigated sex differences of the baseline depression-like behaviors in adult mice using these three strains. Similar to the results in young mice, no difference was found between adult male and female mice in behavioral tests measuring despair in both tail suspension and forced swim tests, and anhedonia in the sucrose preference test. We then extended our study and tested apathy, another endophenotype of depression, using the splash test. Adult male and female mice showed significantly different results in the baseline apathy-like behaviors depending on the investigated strain. This study dissects the complex sex effects of different depression endophenotypes, stresses the importance of considering strain, and puts forward a hypothesis of the inconsistency of results between different laboratories investigating rodent models of depression.

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.

Rationale Unconditioned tasks in rodents have been the mainstay of behavioural assessment for decades, but their validity and sensitivity to detect the behavioural consequences of early life stress (ELS) remains contentious and highly variable. Objectives In the present study, we carried out a meta-analysis to investigate whether persistent behavioural effects, as assessed using unconditioned procedures in rats, are a reliable consequence of early repeated maternal separation, a commonly used procedure in rodents to study ELS. Methods A literature search identified 100 studies involving maternally separated rats and the following unconditioned procedures: the elevated plus maze (EPM); open field test (OFT); sucrose preference test (SPT) and forced swim task (FST). Studies were included for analysis if the separation of offspring from the dam was at least 60 min every day during the pre-weaning period prior to the start of adolescence. Results Our findings show that unconditioned tasks are generally poor at consistently demonstrating differences between control and separated groups with pooled effect sizes that were either small or non-existent (EPM: Hedge’s g =  − 0.35, p  = 0.01, OFT: Hedge’s g =  − 0.32, p  = 0.05, SPT: Hedge’s g =  − 0.33, p  = 0.21, FST: Hedge’s g = 0.99, p  = 0.0001). Despite considerable procedural variability between studies, heterogeneity statistics were low; indicating the lack of standardization in the maternal separation protocol was the not the cause of these inconsistent effects. Conclusions Our findings indicate that in general, unconditioned tests of depression and anxiety are not sufficient to reveal the full behavioural repertoire of maternal separation stress should not be relied upon in isolation. We argue that more objective tasks that sensitively detect specific cognitive processes are better suited for translational research on stress-related disorders such as depression.

This study aimed to examine the antidepressant properties of apigenin in an experimental mouse model of chronic mild stress (CMS). Three weeks following CMS, albino mice of either sex were tested for their antidepressant effects using the tail suspension test (TST) and the sucrose preference test. The percentage preference for sucrose solution and the amount of time spent immobile in the TST were calculated. The brain malondialdehyde (MDA) levels, catalase activity, and reduced glutathione levels were checked to determine the antioxidant potential of treatments. When compared to the control, animals treated with apigenin during the CMS periods showed significantly shorter TST immobility times. Apigenin administration raised the percentage preference for sucrose solution in a dose-dependent manner, which put it on par with the widely used antidepressant imipramine. Animals treated with apigenin displayed a significantly (p ˂ 0.05) greater spontaneous locomotor count (281) when compared to the vehicle-treated group (245). Apigenin was also highly effective in significantly (p ˂ 0.01) lowering plasma corticosterone levels (17 vs. 28 µg/mL) and nitrite (19 vs. 33 µg/mL) produced by CMS in comparison to the control group. During CMS, a high dose (50 mg/kg) of apigenin was given, which greatly increased the reduced glutathione level while significantly decreasing the brain’s MDA and catalase activity when compared to the control group. As a result, we infer that high doses of apigenin may have potential antidepressant effects in animal models via various mechanisms.

Background The chronic unpredictable mild stress (CUMS) model has long been considered the best model for exploring the pathophysiological mechanisms underlying depression. However, there are no widely recognised standards for strategies for modeling and for behavioral testing. The present study aimed to optimize the protocols for food deprivation and the sucrose preference test (SPT) for the CUMS model. Methods We first evaluated the effects of different long periods of food deprivation on the body weight of Sprague Dawley (SD) rats by testing food deprivation for 24 hours (8:00‐8:00+), food deprivation for 12 hours during the daytime (8:00‐20:00) and food deprivation for 12 hours at night (20:00‐8:00+). Next, we established a SD rat CUMS model with 15 different stimulations, and used body weight measurement, SPT, forced swim test (FST), open field test (OFT) and Morris water maze (MWM) test to verify the success of the modeling. In the SPT, consumption of sucrose and pure water within 1 and 12 hours was measured. Results Twelve hours of food deprivation during the daytime (8:00‐20:00) had no effect on body weight, while 12 hours of food deprivation at night (20:00‐8:00+) and 24 hours of food deprivation (8:00‐8:00+) significantly reduced the mean body weight of the SD rats. When SPT was used to verify the successful establishment of the CUMS rat model, sucrose consumption measured within 12 hours was less variable than that measured within 1 hour. Conclusions Twelve hours of food deprivation in the daytime (8:00‐20:00) may be considered a mild stimulus for the establishment of a CUMS rat model. Measuring sucrose consumption over 12 hours is recommended for SPT.

This review describes the role of social isolation in the development of anxiety and depression-like behavior in rodents. The duration of social isolation, age from onset of social isolation, sex, species, and strain of animals, the nature of the model used, and other factors have been shown to have influences. The molecular-cellular mechanisms of development of anxiety and depression-like behavior under the influence of social isolation and the roles of the HHAS, oxidative and nitrosative stress, neuroinflammation, BDNF, neurogenesis, synaptic plasticity, as well as monoamines in these mechanisms are discussed. This review presents data on sex differences in the effects of social isolation, along with the effects of interactions with other types of stress, and the roles of an enriched environment and other factors in ameliorating the negative sequelae of social isolation.

Depression is a common non-motor symptom in Parkinson’s disease (PD) that includes anhedonia and impacts quality of life but is not effectively treated with conventional antidepressants clinically. Vagus nerve stimulation improves treatment-resistant depression in the general population, but research about its antidepressant efficacy in PD is limited. Here, we administered peripheral non-invasive focused ultrasound to hemiparkinsonian (‘PD’) and non-parkinsonian (sham) rats to mimic vagus nerve stimulation and assessed its antidepressant-like efficacy. Following 6-hydroxydopamine (6-OHDA) lesion, akinesia-like immobility was assessed in the limb-use asymmetry test, and despair- and anhedonic-like behaviors were evaluated in the forced swim test and sucrose preference test, respectively. After, tyrosine hydroxylase immuno-staining was employed to visualize and quantify dopaminergic degeneration in the substantia nigra pars compacta, ventral tegmental area, and striatum. We found that PD rats exhibited akinesia-like immobility and > 90% reduction in tyrosine hydroxylase immuno-staining ipsilateral to the lesioned side. PD rats also demonstrated anhedonic-like behavior in the sucrose preference test compared to sham rats. No 6-OHDA lesion effect on immobility in the forced swim test limited conclusions about the efficacy of ultrasound on despair-like behavior. However, ultrasound improved anhedonic-like behavior in PD rats and this efficacy was sustained through the end of the 1-week recovery period. The greatest number of animals demonstrating increased sucrose preference was in the PD group receiving ultrasound. Our findings here are the first to posit that peripheral non-invasive focused ultrasound to the celiac plexus may improve anhedonia in PD with further investigation needed to reveal its potential for clinical applicability.

Depression is a major neuropsychiatric disorder, decreasing the ability of hundreds of millions of individuals worldwide to function in social, academic, and employment settings. Beyond the alarming public health problem, depression leads to morbidity across the entire age including adolescence and adulthood. Modeling depression in rodents has been used to understand the pathophysiological mechanisms behind this disorder and create new therapeutics. Although women are two times more likely to be diagnosed with depression compared to men, behavioral experiments on rodent models of depression are mainly performed in males based on the assumption that the estrous cycles in females may affect the behavioral outcome and cause an increase in the intrinsic variability compared to males. Still, the inclusion of female rodents in the behavioral analysis is mandatory to establish the origin of sex bias in depression. Here, we investigated the baseline depression-like behaviors in male and female mice of three adolescent wild-type inbred strains, C57BL/6N, DBA/2, and FVB/N, that are typically used as background strains for mouse models of neuropsychiatric disorders. Our experiments, performed at two different developmental stages during adolescence (P22–P26 and P32–P36), revealed strain but no sex differences in a set of depression-related tests, including tail suspension, sucrose preference and forced swim tests. Additionally, the 10-day interval during this sensitive period uncovered a strong impact on the behavioral outcome of C57BL/6N and FVB/N mice, highlighting a significant effect of maturation on behavioral patterns. Since anxiety-related behavioral tests are often performed together with depression tests in mouse models of neuropsychiatric disorders, we extended our study and included hyponeophagia as an anxiety test. Consistent with a previous study revealing sex differences in other anxiety tests in adolescent mice, male and females mice behaved differently in the hyponeophagia test at P27. Our study gives insight into the behavioral experiments assessing depression and stresses the importance of considering strain, age and sex when evaluating neuropsychiatric-like traits in rodent models.

The effects of voluntary wheel-running exercise in different rodent models of depression remain unclear, and further research is needed to fully understand the mechanisms underlying these effects. Therefore, this systematic review aimed to evaluate the currently available findings on whether voluntary wheel-running exercise can alleviate depressive symptoms in five different rodent models of depression. The findings of the comprehensive meta-analysis imply that engaging in voluntary wheel-running exercise has a beneficial effect on alleviating depressive symptoms in rodent models that simulate depression. While further research is needed to fully understand the mechanisms and limitations of this intervention future research should aim to conduct larger. Well-designed studies that use standardized protocols and outcome measures. This would help to reduce heterogeneity between studies and improve the overall quality of the evidence base. Additionally, studies should explore the potential mechanisms of action of voluntary wheel-running exercise in treating depression, such as changes in neurotransmitter levels, neuroplasticity, and inflammation. The results suggest that it may hold promise as an adjunctive therapy for depression.