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
Anahita Bahrami, Batool Ghorbani Yekta, Anita Baghdasarians
IBRO Neuroscience Reports July 24, 2026 DOI: 10.1016/j.ibneur.2026.07.010 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Male and female rats |
| Interventions | Ketamine Chlorogenic acid |
| Dose | Ketamine 30 mg/kg, i.p.; Chlorogenic acid 150 mg/kg orally |
| Duration | Ketamine injected for 7 consecutive days; chlorogenic acid administered once 24 h after the last ketamine injection |
| Topics | Esketamine Ketamine |
| Key findings | Chlorogenic acid produced partial and sex-dependent protection against selected ketamine-induced behavioral and molecular changes in rats. It reduced ketamine-induced hyperlocomotion only in males, attenuated increased grooming and reduced forced-swim immobility only in females, and partially lessened novel object recognition impairment and prefrontal BDNF reduction in both sexes. Rearing deficits in males were not reversed. |
Abstract
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.
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
Cites 19
- 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
- Sex difference alters the behavioral and cognitive performance in a rat model of schizophrenia induced by sub-chronic ketamine. Journal of Psychiatric Research October 1, 2024
- NMDA receptor modulation by Esculetin: Investigating behavioral, biochemical and neurochemical effects in schizophrenic mice model. Saudi Pharmaceutical Journal April 1, 2024
- 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
- Ketamine and olanzapine alter behaviour and prefrontal-cortex BDNF differentially in male and female rats Scientific Reports August 23, 2025
and 14 more in the library