Journal
EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE
Volume 266, Issue 7, Pages 673-677Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s00406-015-0649-2
Keywords
Minocycline; MK-801; Caspase-3; Neurotoxicity; Neurodevelopment; Schizophrenia
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Funding
- Olympia-Morata-Programm of the Medical Faculty of the University of Heidelberg
- Sonder-forschungsbereich (SFB) [636/B03]
- German Ministry of Education and Research (BMBF) [01GQ1003B]
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NMDA receptor (NMDAR) antagonists induce in perinatal rodent cortical apoptosis and protracted schizophrenia-like alterations ameliorated by antipsychotic treatment. The broad-spectrum antibiotic minocycline elicits antipsychotic and neuroprotective effects. Here we tested, if minocycline protects also against apoptosis triggered by the NMDAR antagonist MK-801 at postnatal day 7. Surprisingly, minocycline induced widespread cortical apoptosis and exacerbated MK-801-triggered cell death. In some areas such as the subiculum, the pro-apoptotic effect of minocycline was even more pronounced than that elicited by MK-801. These data reveal among antipsychotics unique pro-apoptotic properties of minocycline, raising concerns regarding consequences for brain development and the use in children.
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