Related Experiment Video
Updated: Sep 27, 2025
Strategies for Assessing Autistic-Like Behaviors in Mice
Published on: September 20, 2024
Postweaning social isolation and autism-like phenotype: A biochemical and behavioral comparative analysis
Alessandra Caruso1, Laura Ricceri2, Angela Caruso3
1Department of Physiology and Pharmacology "V. Erspamer" University Sapienza of Rome, Italy.
Insights
Postweaning social isolation in mice reduces brain receptors and social behaviors, mimicking autism spectrum disorder traits. This highlights adolescence as a critical period for social development and mental health.
Area of Science:
- Neuroscience
- Developmental Psychology
- Animal Models
Background:
- Adolescence is a crucial phase for brain maturation.
- Adolescent disturbances increase the risk of neuropsychiatric disorders.
Purpose of the Study:
- To compare the effects of postweaning social isolation (PWSI) on C57BL/6N mice with BTBR mice, a model for autism spectrum disorders (ASD).
- To investigate the biochemical and behavioral changes induced by adolescent social isolation.
Main Methods:
- Male C57BL/6N mice were group-housed or socially isolated for four weeks post-weaning.
- Male BTBR mice, a model of ASD, were analyzed at 48 days of age.
- Biochemical analyses included hippocampal receptor levels (mGlu2, glucocorticoid, mineralocorticoid) and plasma corticosterone.
- Behavioral tests assessed social investigation and ultrasonic vocalizations.
Main Results:
- PWSI reduced hippocampal levels of metabotropic glutamate 2 (mGlu2) receptors, and glucocorticoid and mineralocorticoid receptors.
- BTBR mice showed similar receptor reductions and increased plasma corticosterone.
- Both PWSI mice and BTBR mice exhibited reduced social investigation and ultrasonic vocalizations, indicating lower social responsiveness.
Conclusions:
- Adolescent social isolation induces an endophenotype with social deficits.
- This induced phenotype resembles the behavioral characteristics of the BTBR mouse model of autism spectrum disorders.
- The findings underscore the importance of social stimuli during adolescence for healthy neurodevelopment and mental health.
Abstract:
Adolescence is a critical period for brain development. In most mammalian species, disturbances experienced during adolescence constitute a risk factor for several neuropsychiatric disorders. In this study, we compared the biochemical and behavioral profile induced by postweaning social isolation (PWSI) in inbred C57BL/6 N mice with that of BTBR mice, a rodent model of autism spectrum disorders. Male C57BL/6 N mice were either housed in groups of four or isolated from weaning (postnatal day 21) for four weeks before experimental analyses. After weaning, male BTBR mice were housed four per cage and analyzed at 48 days of age. PWSI reduced hippocampal levels of type 2 metabotropic glutamate (mGlu2) receptors, and glucocorticoid and mineralocorticoid receptors. A similar reduction was seen in group-housed BTBR mice. Plasma corticosterone levels in basal conditions were not influenced by PWSI, but were increased in BTBR mice. Social investigation (total and head sniffing) and the number of ultrasonic vocalizations were reduced in both PWSI mice and age-matched group-housed BTBR mice, indicating a lower social responsiveness in both groups of mice. These results suggest that absence of social stimuli during adolescence induces an endophenotype with social deficit features, which mimics the phenotype of a mouse model of autism spectrum disorders.
