Ketamine-induced behavioural and brain oxidative changes in mice: an assessment of possible beneficial effects of zinc as mono- or adjunct therapy.
Olakunle James Onaolapo, Olayemi Quyyom Ademakinwa, Temitayo Opeyemi Olalekan, Adejoke Yetunde Onaolapo
Psychopharmacology September 2017 DOI: 10.1007/s00213-017-4666-x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled experimental animal study Peer reviewed |
|---|---|
| Population | Male mice weighing 18-20 g |
| Interventions | Zinc Haloperidol Olanzapine Ketamine |
| Duration | 10-day ketamine pretreatment followed by 14-day treatment (days 11-24); behaviors assessed on days 11 and 24 |
| Topics | Ketamine Esketamine |
| Keywords | Antipsychotic Memory Oxidative stress Schizophrenia Social interaction Trace element |
| Key findings | Ketamine increased open-field behaviors, nitric oxide, and MDA while decreasing working memory, social interaction, and glutathione in mice. Zinc alone or with haloperidol or olanzapine was associated with variable degrees of reversal of these effects. The authors propose zinc may have potential as a therapeutic agent or adjunct for schizophrenia-like behavioral and brain oxidative changes. |
Abstract
We studied the influence of zinc, haloperidol or olanzapine on neurobehaviour (open-field, radial arm maze and elevated plus maze) and brain antioxidant status in vehicle- or ketamine-treated mice, with the aim of ascertaining the potentials of zinc in counteracting ketamine's effects. Experiment 1 assessed the effects of zinc in healthy animals and the relative degrees of modulation of ketamine's effects by zinc, haloperidol or olanzapine, respectively. Experiment 2 assessed the modulation of ketamine's effects following co-administration of zinc with haloperidol or olanzapine. Male mice weighing 18-20 g each were used. Animals were pretreated with ketamine (except vehicle, zinc, haloperidol and olanzapine controls) for 10 days before commencement of 14-day treatment (day 11-24) with vehicle, zinc, haloperidol or olanzapine (alone or in combination). Ketamine injection also continued alongside zinc and/or standard drugs in the ketamine-treated groups. Zinc, haloperidol and olanzapine were administered by gavage. Treatments were given daily and behaviours assessed on days 11 and 24. On day 24, animals were sacrificed and whole brain homogenates used for estimation of glutathione, nitric oxide and malondialdehyde (MDA) levels. Ketamine increased open-field behaviours, nitric oxide and MDA levels, while it decreased working memory, social interaction and glutathione. Administration of zinc alone or in combination with haloperidol or olanzapine was associated with variable degrees of reversal of these effects. Zinc may have the potential of a possible therapeutic agent and/or adjunct in the reversal of schizophrenia-like changes in behaviour and brain oxidative status.
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 5
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- Drug models of schizophrenia. Therapeutic Advances in Psychopharmacology February 1, 2015
- Prevention and reversal of ketamine-induced schizophrenia related behavior by minocycline in mice: Possible involvement of antioxidant and nitrergic pathways Journal of Psychopharmacology September 17, 2013
- Mechanisms underlying ketamine-induced synaptic depression in rat hippocampus-medial prefrontal cortex pathway. Neuroscience March 17, 2011
- Models of schizophrenia in humans and animals based on inhibition of NMDA receptors. Neuroscience & Biobehavioral Reviews July 1, 2008