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 (opens in new tab)
Study at a glance
AI-extracted from the abstract| 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 Esketamine |
| Keywords | Risperidone Sex difference Schizophrenia research Psychopharmacology Antipsychotic medication |
| Citations | 21 |
| Key findings | 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.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cited by 5
- Brain-derived neurotrophic factor (BDNF) changes in rodent models of schizophrenia induced by ketamine: a systematic review. Naunyn-Schmiedeberg's Archives of Pharmacology February 20, 2025
- Sigma-1 Receptor Activation by Fluvoxamine Ameliorates ER Stress, Synaptic Dysfunction and Behavioral Deficits in a Ketamine Model of Schizophrenia. Journal of Neuroimmune Pharmacology July 25, 2025
- 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 IBRO Neuroscience Reports July 24, 2026
- Baricitinib ameliorates behavioral deficits and NLRP3-related neuroinflammation in a ketamine rat model of schizophrenia: Role of JAK2/STAT3 and PI3K/AKT/mTOR signaling. International Immunopharmacology August 19, 2026
- A systematic review of ketamine's anxiolytic potential in rodent behavioral models of anxiety and PTSD. Pharmacology, Biochemistry, and Behavior February 2026
Cites 11
- Ketamine use: a review Addiction July 21, 2011
- Psilocybe cubensis extract potently prevents fear memory recall and freezing behavior in short- but not long-term in a rat model of posttraumatic stress disorder. Behavioral Neuroscience January 18, 2024
- The α2C-adrenoceptor antagonist JP-1302 controls behavioral parameters, tyrosine hydroxylase activity and receptor expression in a rat model of ketamine-induced schizophrenia-like deficits. Pharmacology, Biochemistry, and Behavior November 1, 2022
- Role of the NRG1/ErbB4 and PI3K/AKT/mTOR signaling pathways in the anti-psychotic effects of aripiprazole and sertindole in ketamine-induced schizophrenia-like behaviors in rats InflammoPharmacology July 25, 2022
- Schizophrenia-like endurable behavioral and neuroadaptive changes induced by ketamine administration involve Angiotensin II AT1receptor. Behavioural Brain Research February 23, 2022
and 6 more in the library