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.
In a study using adult male Sprague Dawley rats, repeated ketamine administration (30 mg/kg for 5 days) induced social withdrawal and reduced social novelty and motivation, mimicking schizophrenia-like symptoms. Subsequent treatment with either the antipsychotic risperidone (6 mg/kg) or an extract of the herbal plant Salix mucronata (5 mg/kg) for 7 days successfully reversed the social deficits. Both treatments also increased brain dopamine and acetylcholine levels. However, the rats showed reduced sucrose preference (indicating anhedonia) and reduced weight gain after ketamine and mild stress, and reduced brain volume was noted in experimental groups. No differences in brain mass were found between controls and treated groups. The findings suggest that S. mucronata has antipsychotic potential similar to risperidone.