Prevention and reversal of ketamine-induced schizophrenia related behavior by minocycline in mice: Possible involvement of antioxidant and nitrergic pathways.

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.

• Authors: Aline Santos Monte, Greicy Coelho de Souza, Roger S McIntyre, Joanna K Soczynska, Júnia Vieira dos Santos, Rafaela Carneiro Cordeiro, Bruna Mara Machado Ribeiro, David Freitas de Lucena, Silvânia Maria Mendes Vasconcelos, Francisca Cléa Florenço de Sousa, André Férrer Carvalho, Danielle S Macêdo
• Journal: Journal of psychopharmacology (Oxford, England) (J Psychopharmacol) Vol. 27 Issue 11 Pg. 1032-43 (Nov 2013) ISSN: 1461-7285 [Electronic] United States
• PMID: 24045882 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Antipsychotic Agents
• Nitrites
• Thiobarbituric Acid Reactive Substances
• Nitric Oxide
• Ketamine
• Minocycline
• Glutathione
• Risperidone

Topics

• Animals
• Antioxidants (metabolism, pharmacology, therapeutic use)
• Antipsychotic Agents (pharmacology, therapeutic use)
• Corpus Striatum (metabolism)
• Drug Therapy, Combination
• Glutathione (metabolism)
• Hippocampus (drug effects, metabolism)
• Ketamine
• Male
• Maze Learning
• Mice
• Minocycline (pharmacology, therapeutic use)
• Motor Activity (drug effects)
• Nitric Oxide (metabolism)
• Nitrites (analysis)
• Prefrontal Cortex (drug effects, metabolism)
• Risperidone (pharmacology, therapeutic use)
• Schizophrenia (drug therapy, metabolism, prevention & control)
• Schizophrenic Psychology
• Sensory Gating (drug effects)
• Social Behavior
• Thiobarbituric Acid Reactive Substances (metabolism)