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Updated: Jul 10, 2026
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Social Defeat Stress Model for Adolescent C57BL/6 Male and Female Mice
Published on: March 15, 2024
Long-term effects of adolescent risperidone treatment on the mouse cortex
Abneil D Alicea-Pauneto1,2, Hyowon Choi1,2,3, Wenyu Zhang1,2
1Department of Neuroscience, Thomas Jefferson University, Philadelphia, PA, USA.
Summary
Adolescent antipsychotic treatment with risperidone may cause lasting neurodevelopmental changes. This study found altered neuronal function and gene expression in mice, suggesting impacts on brain connectivity and behavior.
Area of Science:
- Neuroscience
- Developmental Psychology
- Pharmacology
Background:
- Second-generation antipsychotics are increasingly prescribed for children and adolescents.
- Concerns exist regarding long-term impacts on neurodevelopment due to receptor blockade.
- Previous rodent studies indicated persistent neurocognitive deficits after adolescent antipsychotic treatment.
Purpose of the Study:
- To investigate the neurobiological underpinnings of long-term neurodevelopmental effects of adolescent risperidone treatment.
- To examine behavioral and neurobiological outcomes following adolescent exposure to risperidone in mice.
- To identify lasting transcriptomic and functional changes in the brain.
Main Methods:
- Adolescent C57BL/6 mice (3-6 weeks) were administered risperidone.
- Behavioral tests assessed anxiety-like behaviors.
- In vivo two-photon calcium imaging and single-nucleus RNA-sequencing (snRNA-seq) were employed post-treatment.
Main Results:
- Risperidone-treated mice showed subtle anxiety-like behavior deficits.
- Increased cortical neuronal calcium event amplitude and altered frequency were observed.
- snRNA-seq revealed reduced potassium channel and NMDA receptor subunit transcripts, indicating weakened synaptic connectivity.
Conclusions:
- Adolescent risperidone treatment induces persistent transcriptomic and functional alterations in neuronal excitability and synaptic connectivity.
- Sex-specific differences in gene expression correlations were noted.
- These changes may underlie cognitive and behavioral dysregulations observed in neurodevelopment.
