In a rat model of schizophrenia induced by five daily injections of ketamine (30 mg/kg), recognition memory was impaired and brain-derived neurotrophic factor (BDNF) levels in the prefrontal cortex decreased in both sexes. Ketamine also lowered pain threshold in females, increased rearing behavior in males, and caused greater hyperlocomotion in females. Subsequent treatment with risperidone (2 mg/kg) restored or attenuated all these behavioral effects and BDNF levels. The findings suggest sex differences in how ketamine affects pain perception, locomotion, and rearing behavior in this model.
A systematic review of 17 rodent studies found that ketamine's effects on brain-derived neurotrophic factor (BDNF) depend on treatment duration, species, and sex. Sub-chronic and chronic ketamine treatment decreased BDNF or had no effect in rats, and decreased BDNF in mice. Acute ketamine treatment commonly increased BDNF. One study reported inconsistent BDNF changes between male and female rats. Due to high methodological variability, there is currently no standardized method for using ketamine as a rodent model of schizophrenia.