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

Eur Arch Psychiatry Clin Neurosci. 2016 Oct;266(7):673-7. doi: 10.1007/s00406-015-0649-2. Epub 2015 Oct 19.

Abstract

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.

Keywords: Caspase-3; MK-801; Minocycline; Neurodevelopment; Neurotoxicity; Schizophrenia.

MeSH terms

  • 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*
  • Mice
  • Mice, Inbred C57BL
  • Minocycline / administration & dosage
  • Minocycline / pharmacology*
  • Neurons / drug effects*
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / pharmacology*
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*

Substances

  • Anti-Bacterial Agents
  • Excitatory Amino Acid Antagonists
  • Neuroprotective Agents
  • Receptors, N-Methyl-D-Aspartate
  • Dizocilpine Maleate
  • Minocycline