Social interaction assessment in rodents: Positive control validation of automated three-chambered social interaction test in rats

SOT 2025 -- Social interactions are fundamental and adaptive components of the biology of numerous species. The integrity of social interaction behavior is critical in maintaining social skills, interpersonal functioning and effective social relationships that define societies. Deficits in social behavior and social recognition are well-recognized in several neuropsychiatric disorders, such as autism spectrum disorders, bipolar disorders, depression, obsessive-compulsive disorders and schizophrenia. Valproic acid, used for bipolar disorders and epilepsy, can increase autism spectrum disorder risk in children when mothers are exposed during pregnancy. Anesthetics like propofol can also heighten neuropsychiatric disorder risk due to N-methyl-D-aspartic acid (NMDA) antagonism and gamma-aminobutyric acid (GABA) activity during early brain development. Complex behavioral tests, like social interaction tests, can vary based on testing conditions and laboratory proficiency. OECD guidelines emphasize that laboratories must demonstrate their capability and the sensitivity of procedures for neurotoxicity and reproductive toxicity assessments. This study aims to validate social interaction assessments using positive controls to demonstrate the reliability and reproducibility of behavior assays in preclinical safety evaluation studies.