Prevention and reversal of ketamine-induced schizophrenia related behavior by minocycline in mice: Possible involvement of antioxidant and nitrergic pathways
Aline Santos Monte, Greicy Coelho de Souza, Roger S McIntyre, Joanna K. Soczynska, Junia Vieira Dos Santos, R.C. Cordeiro, Bruna Mara Machado Ribeiro, David Freitas de Lucena, Silvânia Maria Mendes Vasconcelos, Francisca Cléa Florenço de Sousa, André F. Carvalho, Danielle S. Macêdo
Journal of Psychopharmacology September 17, 2013 DOI: 10.1177/0269881113503506 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | Minocycline Risperidone Ketamine |
| Dose | Ketamine 20 mg/kg per day intraperitoneally; minocycline 25 or 50 mg/kg daily |
| Duration | 14 days |
| Measures | Locomotor activity, prepulse inhibition of startle, social interaction, Y maze, glutathione (GSH), thiobarbituric acid-reactive substances (TBARS), nitrite levels |
| Topics | Ketamine Esketamine |
| Keywords | Minocycline Tbars Prepulse inhibition Pharmacology Schizophrenia object-oriented programming Clozapine Oxidative stress Lipid peroxidation Biochemistry |
| Citations | 123 |
| Key points | Minocycline prevented and reversed ketamine-induced behavioral and oxidative changes in mice, comparable to risperidone. |
Abstract
It has been hypothesized that oxidative imbalance and alterations in nitrergic signaling play a role in the neurobiology of schizophrenia. Preliminary evidence suggests that adjunctive minocycline treatment is efficacious for cognitive and negative symptoms of schizophrenia. This study investigated the effects of minocycline in the prevention and reversal of ketamine-induced schizophrenia-like behaviors in mice. In the reversal protocol, animals received ketamine (20 mg/kg per day intraperitoneally or saline for 14 days, and minocycline (25 or 50 mg/kg daily), risperidone or vehicle treatment from days 8 to 14. In the prevention protocol, mice were pretreated with minocycline, risperidone or vehicle prior to ketamine. Behaviors related to positive (locomotor activity and prepulse inhibition of startle), negative (social interaction) and cognitive (Y maze) symptoms of schizophrenia were also assessed. Glutathione (GSH), thiobarbituric acid-reactive substances (TBARS) and nitrite levels were measured in the prefrontal cortex, hippocampus and striatum. Minocycline and risperidone prevented and reversed ketamine-induced alterations in behavioral paradigms, oxidative markers (i.e. ketamine-induced decrease and increase in GSH levels and TBARS content, respectively) as well as nitrite levels in the striatum. These data provide a rationale for evaluating minocycline as a novel psychotropic agent and suggest that its mechanism of action includes antioxidant and nitrergic systems.
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 20
- Drug models of schizophrenia. Therapeutic Advances in Psychopharmacology February 1, 2015
- Effective action of silymarin against ketamine-induced schizophrenia in male mice: Insight into the biochemical and molecular mechanisms of action. Journal of Psychiatric Research November 1, 2024
- Delayed emergence of behavioral and electrophysiological effects following juvenile ketamine exposure in mice Translational Psychiatry September 15, 2015
- Inhibition of oxidative stress, neuroinflammatory cytokines, and protein expressions contributes to the antipsychotic effects of geraniol in mice with ketamine-induced schizophrenia. Journal of Neuroimmune Pharmacology July 3, 2025
- Exploring the interplay of chronic toxoplasmosis and NMDAR dysfunction: Insights into schizophrenia-like behaviors and therapeutic potential. Open veterinary journal July 1, 2024
and 15 more in the library
Cites 4
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- Has an angel shown the way? Etiological and therapeutic implications of the PCP/NMDA model of schizophrenia. Schizophrenia Bulletin September 1, 2012
- Mechanisms underlying ketamine-induced synaptic depression in rat hippocampus-medial prefrontal cortex pathway. Neuroscience March 17, 2011
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