Brain-derived neurotrophic factor (BDNF) changes in rodent models of schizophrenia induced by ketamine: a systematic review.
Atefeh Motamedi-Manesh, Mahdieh Farzin Asanjan, Hamed Fallah, Shahrzad Gharibian, Alireza Taghavi, Zahra Haghighi Poode, Shahin Akhondzadeh, Salar Vaseghi
Naunyn-Schmiedeberg's Archives of Pharmacology February 20, 2025 DOI: 10.1007/s00210-025-03912-7 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Peer reviewed |
|---|---|
| Population | Rodents (rats and mice) |
| Intervention | Ketamine |
| Topics | Ketamine Esketamine |
| Keywords | Mice Rats Systematic review Schizophrenia research Psychopharmacology Animal studies Brain proteins |
| Citations | 6 |
| Key findings | Ketamine's effects on BDNF in rodent models of schizophrenia vary by treatment duration, species, and sex, with no standardized method currently available. |
Abstract
Schizophrenia is a severe neuropsychiatric disorder ranking among the top ten global disability causes. In rodents, sub-chronic or chronic ketamine treatment is used for the induction of schizophrenia. Ketamine affects the function of brain-derived neurotrophic factor (BDNF), the most important neurotrophin involved in the pathophysiology of different neuropsychiatric disorders. The present systematic review aimed to investigate BDNF changes in rodent studies used ketamine-induced schizophrenia. PubMed electronic database was searched and 44 articles were found. After removal of unrelated articles, 17 articles were selected. The results showed a wide range of inconsistent changes in BDNF levels. We found that sub-chronic and chronic ketamine treatment in rats decreased BDNF or had no effect. Sub-chronic and chronic ketamine treatment in mice only decreased BDNF. However, increased BDNF was commonly observed following acute ketamine treatment. These results showed the possible role of species and the duration of treatment. Also, sex can also be involved in BDNF changes because one study showed inconsistent BDNF changes in male and female rats. In conclusion, we found that ketamine's effects may depend on factors such as duration of administration, sex, and species. Therefore, the wide range of BDNF changes may be related to high variability in methods. Because of this variability, there is currently no standardized method for using ketamine as a rodent model for schizophrenia. Further research is needed to establish a standardized pharmacological model of schizophrenia using ketamine treatment.
Comparable studies
Other systematic reviews and meta-analyses on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis Depressed patients with suicidal ideation at baseline | 2017 | Systematic review and individual participant data meta-analysis | n = 167 |
| Ketamine use: a review Ketamine users | 2011 | Systematic review | |
| Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression Participants with major depression in placebo-controlled, double-blind, randomized... | 2015 | Systematic review and meta-analysis | |
| Ketamine and postoperative pain – a quantitative systematic review of randomised trials Surgical patients from 25 countries | 2004 | Systematic review | n = 2,839 |
| Side-effects associated with ketamine use in depression: a systematic review. Patients with depression | 2018 | Systematic review |
Citations in the library
Cited by 2
- 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
- Revealing shortcomings in the assessment of psilocybin effects on OCD-related symptoms in preclinical and clinical studies: A systematic review Journal of Affective Disorders Reports June 8, 2026
Cites 16
- Recent advances in the phencyclidine model of schizophrenia American Journal of Psychiatry October 1, 1991
- Study of a New Schizophrenomimetic Drug—Sernyl Archives of Neurology And Psychiatry March 1, 1959
- Ketamine and rapid antidepressant action: new treatments and novel synaptic signaling mechanisms Neuropsychopharmacology July 24, 2023
- Microglial ERK-NRBP1-CREB-BDNF signaling in sustained antidepressant actions of (R)-ketamine Molecular Psychiatry November 24, 2021
- Ketamine for the treatment of mental health and substance use disorders: comprehensive systematic review BJPsych Open December 23, 2021
and 11 more in the library