Serotonin Signaling and Behavioral Dynamics in Animal Models

Serotonin (5-hydroxytryptamine, 5-HT) is a key neuromodulator that orchestrates a broad spectrum of behaviours in vertebrates, including aggression, anxiety, social interaction and cognitive flexibility. In vivo studies employing rodents and other small mammals have revealed how distinct 5-HT receptor subtypes influence neural circuit function and consequent behavioural outputs. Genetic and pharmacological manipulations of serotonin synthesis, reuptake and receptor expression have been complemented by advanced tools such as optogenetics and in vivo imaging, offering unprecedented spatiotemporal resolution. Converging evidence highlights that serotonin signalling does not act in isolation but interacts with neurotrophic factors, intracellular stress pathways and transcriptional regulators to shape synaptic plasticity and emotional reactivity. Behavioural assays—from the forced swim test to approach–avoidance paradigms—have elucidated how alterations in 5-HT dynamics translate into resilient or maladaptive coping strategies. Together, these animal-model investigations underpin our understanding of psychiatric disorders and guide the development of novel therapeutic approaches that target specific nodes within the serotonin network.

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Serotonin Signaling and Behavioral Dynamics in Animal Models publication trend

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

Technical terms

Serotonergic neurotransmission: The process by which serotonin is synthesised from tryptophan, released into the synaptic cleft, binds to postsynaptic or presynaptic receptors and is then removed by reuptake or enzymatic degradation.

5-HT receptor subtypes: A family of G-protein-coupled and ligand-gated receptors (e.g. 5-HT1A, 5-HT2A, 5-HT7) that mediate diverse intracellular signalling cascades and behavioural effects.

Brain-derived neurotrophic factor (BDNF): A neurotrophin that supports neuronal survival, differentiation and synaptic plasticity, interacting with serotonin pathways to influence mood and aggression.

Cerebral dopamine neurotrophic factor (CDNF): An endoplasmic-reticulum-resident protein that regulates unfolded-protein-response pathways and modulates monoamine metabolism, including serotonin turnover.

Serotonin turnover: The rate at which serotonin is metabolised to its principal breakdown product, 5-hydroxyindoleacetic acid (5-HIAA), serving as a functional index of serotonergic activity.

References

1. On Associations between Fear-Induced Aggression, Bdnf Transcripts, and Serotonin Receptors in the Brains of Norway Rats: An Influence of Antiaggressive Drug TC-2153. International Journal of Molecular Sciences (2023).
2. The Implication of 5-HT Receptor Family Members in Aggression, Depression and Suicide: Similarity and Difference. International Journal of Molecular Sciences (2022).
3. CDNF Exerts Anxiolytic, Antidepressant-like, and Procognitive Effects and Modulates Serotonin Turnover and Neuroplasticity-Related Genes. International Journal of Molecular Sciences (2024).