Investigating the effects of chlorogenic acid on novel object recognition memory impairment, hyperlocomotion, and prefrontal BDNF expression in a sub-chronic ketamine-induced schizophrenia-like rat model.

Schizophrenia is a severe neuropsychiatric disorder characterized by positive, negative, cognitive, mood-related, and motor symptoms. Sub-chronic ketamine administration is widely used to induce schizophrenia-like behavioral and cognitive alterations in rodents. Chlorogenic acid (CGA) is an abundant dietary phenolic acid with reported anti-inflammatory, antioxidative, and neuroprotective properties. The present study examined the effects of CGA on behavioral disturbances in male and female rats exposed to sub-chronic ketamine administration, together with brain-derived neurotrophic factor (BDNF) expression in the prefrontal cortex. Ketamine was injected for 7 consecutive days (30 mg/kg, i.p.), and CGA was orally administered once (150 mg/kg) 24 h after the last ketamine injection. Ketamine increased locomotor activity in both sexes, with a greater effect in females; CGA partially reduced this effect only in males. Rearing was reduced only in ketamine-treated males, and CGA did not reverse this change. Grooming was increased in both sexes after ketamine administration, whereas CGA attenuated this effect only in females. Novel object recognition memory was impaired in both sexes after ketamine administration, and CGA partially attenuated this impairment. Immobility in the forced swim test was reduced only in ketamine-treated females, and CGA attenuated this effect. Prefrontal BDNF expression was decreased after ketamine administration in both sexes, and CGA partially attenuated this reduction. Overall, CGA showed partial and sex-dependent protective effects against selected ketamine-induced behavioral and molecular alterations. These findings should be interpreted in light of the absence of independent DMSO-only vehicle-control cohorts.