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 via OpenAlex
Summary
AI-generated from the abstractMinocycline, an antibiotic, prevented and reversed schizophrenia-like behaviors in mice given ketamine, including changes in movement, startle response, social interaction, and memory. It also corrected ketamine-induced oxidative stress—lowered glutathione and raised lipid peroxidation markers—and altered nitrite levels in the striatum. The effects were similar to those of the antipsychotic risperidone. The findings suggest minocycline's potential as a novel psychotropic agent, with its mechanism involving antioxidant and nitrergic systems.
Study at a glance
| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | Minocycline Risperidone |
| Dose | 25 or 50 mg/kg daily |
| Duration | 14 days |
| Topics | Ketamine |
| Keywords | Minocycline Tbars Prepulse inhibition Pharmacology |
| Citations | 123 |
| Key finding | 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.