Sex difference alters the behavioral and cognitive performance in a rat model of schizophrenia induced by sub-chronic ketamine.
Mohammad-Ali Samizadeh, Seyedeh-Tabassom Abdollahi-Keyvani, Hamed Fallah, Bahar Beigi, Atefeh Motamedi-Manesh, Sogand Adibian, Salar Vaseghi
Journal of psychiatric research October 1, 2024 DOI: 10.1016/j.jpsychires.2024.08.014 via PubMed
Summary
AI-generated from the abstractIn 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.
Study at a glance
| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | Ketamine Risperidone |
| Dose | 30 mg/kg ketamine, 2 mg/kg risperidone |
| Duration | Five consecutive days |
| Topics | Ketamine |
| Keywords | Risperidone Sex difference Schizophrenia research Psychopharmacology |
| Citations | 21 |
| Key finding | Ketamine impaired recognition memory and reduced prefrontal BDNF in both sexes, while risperidone reversed these effects, with sex differences observed in pain threshold, locomotion, and rearing behavior. |
Abstract
Schizophrenia is a complex neuropsychiatric disorder with positive, negative, and cognitive symptoms. In rats, sub-chronic administration of ketamine is used for the induction of schizophrenia model. Increased locomotor activity is one of the most important features of psychotic-like symptoms in rodents. On the other hand, risperidone is a potent antipsychotic medication that is approved for the treatment of schizophrenia and bipolar disorder. In the present research, we aimed to investigate the effect of sub-chronic treatment of ketamine on cognitive and behavioral functions, and brain-derived neurotrophic factor (BDNF) expression level in the prefrontal cortex. Also, we assessed the efficacy of risperidone on cognitive and behavioral impairments induced by ketamine. Possible sex differences were also measured. Ketamine was intraperitoneally injected at the dose of 30 mg/kg for five consecutive days. Risperidone was also intraperitoneally injected at the dose of 2 mg/kg. Novel object recognition memory, pain threshold, locomotor activity, rearing behavior, and BDNF level were evaluated. The results showed that ketamine injection for five consecutive days impaired the acquisition of long-term recognition memory and decreased BDNF level in the prefrontal cortex in both sexes. Also, it decreased pain threshold in females, increased rearing behavior in males, and induced hyperlocomotion with greater effect in females. On the other hand, risperidone restored or attenuated the effect of ketamine on all the behavioral effects and BDNF level. In conclusion, we suggested that there were sex differences in the effects of ketamine on pain perception, locomotion, and rearing behavior in a rat model of schizophrenia.