Vinpocetine halts ketamine-induced schizophrenia-like deficits in rats: impact on BDNF and GSK-3β/β-catenin pathway.
Hebatalla I Ahmed, Somaia A Abdel-Sattar, Heba S Zaky
Naunyn-Schmiedeberg's Archives of Pharmacology August 6, 2018 DOI: 10.1007/s00210-018-1552-y (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Male Sprague-Dawley rats |
| Interventions | Vinpocetine Ketamine Risperidone |
| Dose | Vinpocetine 20 mg/kg i.p.; ketamine 25 mg/kg i.p. |
| Duration | Vinpocetine given once daily for 14 days, starting 7 days before ketamine administration |
| Topics | Ketamine Esketamine |
| Keywords | Hippocampus Animals Rats, sprague-dawley Malondialdehyde Vinca alkaloids Brain-derived neurotrophic factor Antipsychotic agents Behavior, animal Schizophrenia Signal transduction Oxidative stress Male Beta catenin Β-catenin Glycogen synthase kinase-3β Vinpocetine |
| Key points | Vinpocetine pretreatment reduced ketamine-induced hyperlocomotion, anxiety, and short-term memory deficits in rats and attenuated hippocampal oxidative stress, inflammation, and neurotransmitter alterations. The authors propose these protective effects may involve elevated BDNF expression and prevention of ketamine-induced GSK-3β/β-catenin pathway activation. |
Abstract
There are increasing evidences supporting the involvement of oxidative stress and neuroinflammation in schizophrenia. Vinpocetine, a nootropic phosphodiesterase-1 inhibitor, was proven to possess anti-oxidant and anti-inflammatory potentials. This research aimed to reveal the likely protective features of vinpocetine against ketamine-induced schizophrenia-like deficits in rats. Additionally, the probable mechanisms contributing to this neuroprotection were also elucidated. Vinpocetine was given (20 mg/kg, i.p.) once a day for 14 days commencing 7 days before administrating ketamine (25 mg/kg i.p.). Risperidone was applied as a reference antipsychotic. Vinpocetine pre-treatment revealed a marked amendment in the hyperlocomotion, anxiety, and short-term memory deficits induced by ketamine in rats. In rats' hippocampus, ketamine induced a drastic increase in tissue levels of dopamine, lipid peroxidation, and pro-inflammatory cytokines along with a significant decrease in glutamate, GABA, SOD, and total anti-oxidant capacity. Also, ketamine induced a reduced level of BDNF together with the potentiation of GSK-3β/β-catenin pathway that led to the destruction of β-catenin. Pre-treatment of ketamine-challenged animals with vinpocetine significantly attenuated oxidative stress, inflammation, and neurotransmitter alterations. Vinpocetine also elevated BDNF expression and prevented ketamine-induced stimulation of the GSK-3β/β-catenin signaling. This research presents enlightenments into the role of vinpocetine in schizophrenia. This role may be accomplished through its effect on oxidative stress, inflammation as well as modulating BDNF and the GSK-3β/β-catenin pathway.
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
- Lithium attenuates ketamine-induced long-term neurotoxicity through DISC1-mediated GSK-3β/β-catenin and ERK/CREB pathways. Toxicology Letters April 1, 2025
- The immune regulatory mechanism of ketamine-induced psychiatric disorders: A new perspective on drug-induced psychiatric symptoms. Progress in Neuro-Psychopharmacology and Biological Psychiatry January 10, 2025
- Inulin ameliorates chronic ketamine-induced anxiety-like behaviors and impairments in spatial learning and memory: involvement of gut microbiota, microbial metabolite short-chain fatty acids, and the BDNF-TrkB-ERK1/2-CREB pathway Frontiers in Microbiology April 7, 2026
- Neuroprotective effects of curcumin-loaded nanophytosome on ketamine-induced schizophrenia-like behaviors and oxidative damage in male mice. Neuroscience Letters September 15, 2021