Minocycline exacerbates apoptotic neurodegeneration induced by the NMDA receptor antagonist MK-801 in the early postnatal mouse brain

• Published in: European archives of psychiatry and clinical neuroscience 2016-10, Vol.266 (7), p.673-677
• Main Authors: Inta, Ioana, Vogt, Miriam A., Vogel, Anne S., Bettendorf, Markus, Gass, Peter, Inta, Dragos
• Format: Article
• Language: English
• Subjects: Animals; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - pharmacology; Apoptosis - drug effects; Brain - drug effects; Brain - pathology; Disease Models, Animal; Dizocilpine Maleate - pharmacology; Excitatory Amino Acid Antagonists - pharmacology; Medicine; Medicine & Public Health; Mice; Mice, Inbred C57BL; Minocycline - administration & dosage; Minocycline - pharmacology; Neurons - drug effects; Neuroprotective Agents - administration & dosage; Neuroprotective Agents - pharmacology; Neurosciences; Psychiatry; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Short Communication
• ISSN: 0940-1334; 1433-8491
• DOI: 10.1007/s00406-015-0649-2

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.