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Rapastinel alleviates the neurotoxic effect induced by NMDA receptor blockade in the early postnatal mouse brain

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Abstract

Rapastinel is a novel psychoactive substance that acts as an N-methyl-D-aspartate-receptor (NMDAR) agonist and triggers antidepressant- and antipsychotic-like effects in animal models. However, it is unknown if rapastinel possesses a better side-effect profile than fast-acting glutamatergic antidepressants, like ketamine, which trigger neurotoxicity in the perinatal rodent cortex and protracted schizophrenia-like alterations. Here we found a remarkable neuroprotective effect of rapastinel against apoptosis induced by the NMDAR antagonist MK-801 in comparison to that elicited by clozapine and the mGlu2/3 agonist LY354740. These results suggest the potential therapeutic/prophylactic effect of rapastinel in ameliorating deleterious effects induced by NMDAR blockade during neurodevelopment.

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Acknowledgements

This work was supported by grants from the Deutsche Forschungsgemeinschaft (DFG) IN 168/3-1, the Ingeborg Ständer Foundation, the ERA-NET NEURON program, the Bundesministerium für Bildung und Forschung (BMBF) under the frame of Neuron Cofund (ERA-NET NEURON NMDAR-PSY) and the Swiss National Foundation (SNF) 186346 to D.I.

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  1. Peter Gass and Dragos Inta have contributed equally to this work.

Authors and Affiliations

  1. RG Animal Models in Psychiatry, Department of Psychiatry and Psychotherapy, Medical Faculty Mannheim, Central Institute of Mental Health Mannheim, Heidelberg University, J 5, 68159, Mannheim, Germany

    Andrei-Nicolae Vasilescu, Anne Mallien, Natascha Pfeiffer, Peter Gass & Dragos Inta

  2. Department of Psychiatry (UPK), University of Basel, Wilhelm Klein Str. 27, 4002, Basel, Switzerland

    Undine E. Lang & Dragos Inta

Authors
  1. Andrei-Nicolae Vasilescu
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  2. Anne Mallien
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  3. Natascha Pfeiffer
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  4. Undine E. Lang
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  5. Peter Gass
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  6. Dragos Inta
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Correspondence to Dragos Inta.

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Vasilescu, AN., Mallien, A., Pfeiffer, N. et al. Rapastinel alleviates the neurotoxic effect induced by NMDA receptor blockade in the early postnatal mouse brain. Eur Arch Psychiatry Clin Neurosci 271, 1587–1591 (2021). https://doi.org/10.1007/s00406-020-01180-5

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  • DOI: https://doi.org/10.1007/s00406-020-01180-5

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