Effects of combined postweaning social isolation and ketamine administration on schizophrenia-like behaviour in male Sprague Dawley rats.
Behavioural brain research January 5, 2025 Khanyiso Bright Shangase, Mluleki Luvuno, Musa Mabandla 6 citations
A double-hit model combining ketamine injections and social isolation in male rats produced stronger negative and cognitive symptoms of schizophrenia than either treatment alone. The isolated rats given ketamine showed high anxiety, elevated stress hormones (ACTH, corticosterone, norepinephrine), reduced social interaction, decreased oxytocin, increased aggression toward a juvenile intruder despite low testosterone, impaired visual learning and memory, and increased proinflammatory cytokines. The findings suggest that combining two schizophrenia-inducing interventions yields a more robust model for studying the neurobiological basis of negative and cognitive symptoms.