# Behavioral manifestations and underlying mechanisms of amphetamine in constructing animal models of mania: a comprehensive review

**Authors:** Zi-Qi Deng, Xiao-Chen Si, Jia-Bin Song, Jin-Yao Li, Lu Sun, Xue Dang, Min Zhao, Yan-Chen Feng, Fei-Xiang Liu

PMC · DOI: 10.3389/fnins.2025.1544311 · Frontiers in Neuroscience · 2025-05-09

## TL;DR

This paper reviews how amphetamine induces mania-like behaviors in animals and explores the underlying brain mechanisms.

## Contribution

The paper provides a comprehensive review of amphetamine-induced mania models and their relevance to understanding human mania.

## Key findings

- Amphetamine causes mania-like behaviors in animals, including increased risk-seeking and locomotion.
- Amphetamine disrupts neurotransmitter balance and increases oxidative stress in brain regions like the frontal cortex.
- Altered signaling pathways and neurotrophin levels in the model suggest links to mania symptoms and cognitive impairment.

## Abstract

Mania is a mind disorder with heightened emotions, etc. Amphetamine (AMPH), a drug with central nervous system excitatory effects, can disrupt neurotransmitter release and metabolism, causing mania. AMPH-induced animal models of mania show increased risk and reward-seeking behaviors and excessive locomotion like mania patients, verifiable by tests like Elevated Plus Maze (EPM). It also impacts neurotransmitter balance in different brain regions, aligning with the imbalance in mania patients. Multiple signaling pathways including extracellular regulated protein kinases and others are involved, and their altered activities link to mania symptoms. In the AMPH-induced mania model, regions like the frontal cortex have increased oxidative stress and inflammatory response. Moreover, AMPH changes neurotrophin levels, potentially causing neuronal damage and cognitive impairment. In summary, the AMPH-induced mania animal model is crucial for studying mania’s pathogenesis. However, further in-depth studies on neurotransmitter regulation, signaling pathway intervention, and neurotrophic factors are needed to develop more effective and personalized treatment plans.

## Linked entities

- **Chemicals:** amphetamine (PubChem CID 3007)

## Full-text entities

- **Diseases:** cognitive impairment (MESH:D003072), inflammatory (MESH:D007249), neuronal damage (MESH:D009410), mind disorder (MESH:D009358), Mania (MESH:D001714)
- **Chemicals:** AMPH (MESH:D000661)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

162 references — full list in the complete paper: https://tomesphere.com/paper/PMC12098516/full.md

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Source: https://tomesphere.com/paper/PMC12098516