Animal Models of Anxiety and Depression

Animal models of anxiety and depression provide indispensable tools for investigating the complex neurobiological and behavioural mechanisms underlying these disorders. Rodent paradigms predominate, encompassing acute pharmacological challenges, genetic manipulations and environmental stressors. Common assays such as the elevated plus maze and open field test probe unconditioned anxiety-like behaviour, while the forced swim and tail suspension tests quantify behavioural despair. Models induced by chronic social defeat, unpredictable mild stress or learned helplessness replicate facets of human mood disorders, including anhedonia, social withdrawal and dysregulated hypothalamic–pituitary–adrenal axis function. Genetic lines selectively bred for high or low trait anxiety and transgenic mice targeting neurotransmitter systems further elucidate circuit-level contributions. Complementary approaches in non-mammalian species, such as zebrafish and Drosophila, exploit high-throughput screening to identify candidate molecules and pathways. Integration of behavioural, molecular and electrophysiological readouts enhances translational validity, paving the way for novel therapeutic strategies. As global mental health burdens escalate, refined animal models offer a platform for dissecting gene–environment interactions, biomarker discovery and the preclinical evaluation of anxiolytic and antidepressant agents.

Research from Nature Portfolio

Integrated proteomic and metabolomic profiling in mice treated chronically with selective serotonin reuptake inhibitors has revealed that purine and pyrimidine metabolism pathways diverge between responders and non-responders. Hippocampal and plasma biosignatures differentiate behavioural outcomes in forced swim paradigms, and corresponding protein levels in peripheral samples correlate with treatment efficacy in humans. These findings suggest that nucleotide metabolism may serve as a potential biomarker for stratifying antidepressant response and guiding personalised interventions.

Animal Models of Anxiety and Depression publication trend

The graph below shows the total number of articles in animal models of anxiety and depression across all publications each year (not limited to Nature Index journals).

Technical terms

Elevated plus maze: A cross-shaped platform with open and enclosed arms used to evaluate anxiety-like behaviour in rodents based on aversion to open spaces.

Forced swim test: A behavioural assay measuring immobility time in water, interpreted as a correlate of behavioural despair and antidepressant efficacy.

Learned helplessness: A paradigm in which animals exhibit failure to escape aversive stimuli after exposure to inescapable stress, modelling anhedonia and motivational deficits.

Trait anxiety: A stable tendency to perceive ambiguous situations as threatening, often assessed through consistent behavioural responses across multiple tests.

Epigenetic mechanism: Heritable modifications of gene expression without altering DNA sequence, including DNA methylation and histone acetylation, influencing stress resilience and vulnerability.

References

1. Purine and pyrimidine metabolism: Convergent evidence on chronic antidepressant treatment response in mice and humans. Scientific Reports (2016).
2. Leveraging interindividual variability in threat conditioning of inbred mice to model trait anxiety. PLOS Biology (2024).
3. Prenatal SAMe Treatment Changes via Epigenetic Mechanism/s USVs in Young Mice and Hippocampal Monoamines Turnover at Adulthood in a Mouse Model of Social Hierarchy and Depression. International Journal of Molecular Sciences (2023).
4. Animal Models of Depression: What Can They Teach Us about the Human Disease?. Diagnostics (2021).