ENRICHED ENVIRONMENT REDUCES ANXIETY-LIKE BEHAVIOUR AND COULD REOPEN PLASTICITY IN SCHIZOPHRENIA-LIKE PHENOTYPE RATS EXPOSED TO SOCIAL INSTABILITY STRESS IN ADOLESCENCE

Schizophrenia (SZ) is a neurodevelopmental disorder emerging at adolescence, characterized among others by anxiety, and impaired sensorimotor gating. Social stress is key in SZ’s etiology, particularly during adolescence by reshaping brain development and increasing vulnerability in susceptible individuals. Environmental interventions like cognitive behavioural therapy (CBT) may reverse these effects. Using a rat model, we investigated whether adolescent social instability stress (SI) induces SZ-relevant behaviours, and whether these effects can be reduced by enriched environment (EE), analogous to human CBT.
Three weeks after the end of a 3-weeks SI protocol during adolescence, anxiety and sensorimotor gating were evaluated to identify rats with SZ-like phenotype. These rats and controls then experienced 3 weeks of EE, with a Marlau’s cage for cognitive and social enrichment, followed by retesting. Immunostaining for parvalbumin and perineuronal nets was performed in the prefrontal cortex (PFC) and ventral hippocampus (vHIP) (Figure 1).

Three weeks after the end of stress, approximately 40% of rats exhibited increased anxiety and impaired sensori-motor gating, reminiscent of SZ symptoms. EE exposure allowed a return to anxiety control levels for SZ-like rats. In vHIP, EE decreased the number of perineuronal nets and those which surrounded parvalbumin-positive cells. Analyses in the PFC are ongoing.
In conclusion, SI during adolescence induces an SZ-like phenotype in some rats. EE restored anxiety to control levels possibly through plastic remodelling of perineuronal nets. This study highlights the impact of environmental interventions such as EE or CBT, although further analyses are needed to clarify underlying mechanisms.