Multidimensional analysis of social withdrawal in the sub-chronic phencyclidine rat model for schizophrenia.

Rats treated with phencyclidine (PCP) to model schizophrenia's negative symptoms showed reduced overall social interaction compared to controls, but the deficit was selective: some behaviors (e.g., Following) were impaired while others were not. A detailed analysis of 42 behaviors revealed that PCP-treated rats also displayed a persistent attentional bias toward the inanimate environment during both habituation and social exposure, suggesting their attention was displaced away from other rats. This multidimensional behavioral approach uncovers a more nuanced phenotype than simple total interaction time, indicating altered attentional allocation as a possible mechanism underlying social withdrawal in this model.

Study at a glance

Abstract

RATIONALE: Social withdrawal in the sub-chronic phencyclidine (PCP) rat model—a behavioral correlate of schizophrenia’s negative symptoms—is well characterized, yet the psychological mechanisms underlying this deficit remain unclear. OBJECTIVES: Despite the complexity of social behavior, assessments often rely on a single metric (e.g., total interaction time) that has limited explanatory power, thus limiting insight into the underlying processes. This study aimed to address this gap through a multidimensional behavioral analysis. METHODS: We developed a detailed ethogram encompassing both social and non-social behaviors (e.g., self-directed actions and environmental exploration) within the dyadic social interaction paradigm. Specifically, we defined 42 behaviors (or behavior groups), 28 of which were social, organized into five categories: Avoidance, Risk Assessment, Approach, Recognition, and Contact. Behavioral scoring was performed manually using ANY-maze and supplemented with automated tracking via EthovisionXT, enabling a comprehensive analysis of saline- and PCP-treated rats (5 mg/kg, twice daily for 7 days, followed by a washout). RESULTS: PCP-treated rats exhibited a significant reduction in overall social interaction compared to controls, with selective impairments in specific behaviors (e.g., Following) but not others. Notably, these animals demonstrated a persistent attentional bias toward the inanimate environment—evident during both habituation and social exposure phases—suggesting a displacement of attention away from conspecific engagement. CONCLUSIONS: Our findings reveal a nuanced behavioral phenotype in PCP-treated rats, characterized not only by reduced social interaction but also by altered attentional allocation. These findings deepen our understanding of the neuropsychological mechanisms underlying PCP-induced social withdrawal and its relevance to schizophrenia.