Early postnatal handling alters social behavior, learning, and memory of pre- and postnatal VPA-induced rat models of autism in a context-based manner

Abstract

Early life events are known to greatly affect brain development, cortical neurogenesis, and Hypothalamic-pituitary-adrenal activity. Mainly characterized by impairment in social communication, language, and cognitive development, autism spectrum disorder (ASD) refers to a class of neuropsychiatric disorders with numerous genetic and environmental risk factors. In the early handling (EH) method, daily separation of infants from their mother, physical touching, and exposure to a new environment occur. Here, we studied the effect of EH on Social interaction, learning, and memory in rats exposed pre-or post-natally to valproic acid (VPA). Gestational VPA exposure (600 mg/kg) led to some severe autistic-like traits, more notable in the social behavior of the male sex, along with unchanged to partially altered spatial learning and memory function and reduced avoidance memory. In comparison, while causing a sex-dependent increase in spatial memory, subcutaneous injection of VPA (400 mg/kg) in infancy resulted in limited adverse autistic features, including a decrease in males’ social preference, as well as reduced avoidance memory. The results indicated that neonatal handling significantly improved multiple social behavior and memory deficits in prenatally injected rats. In contrast, EH in rats receiving postnatal VPA elicited a restricted advantage on social novelty tendency; while negatively affecting some other social behavior criteria and spatial learning of males and encouraging sex-dependent repetitive behaviors in the social setting. The controversial influence of postnatal handling on juvenile rats of postnatal VPA treatment vs. prenatal VPA treatment opens up the potential for future research on the context-based consequence of early-life handling stress using different behavioral tasks and to benefit therapeutic procedures through understanding the sex- and age-specific neurobiology of short-term environmental manipulation in animal models of autism.