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Laha K, Zhu M, Gemperline E, et al. CPP impairs contextual learning at concentrations below those that block pyramidal neuron NMDARs and LTP in the CA1 region of the hippocampus. Neuropharmacology. 2021;202:108846doi: 10.1016/j.neuropharm.2021.108846.
Laha, K., Zhu, M., Gemperline, E., Rau, V., Li, L., Fanselow, M. S., Lennertz, R., & Pearce, R. A. (2022). CPP impairs contextual learning at concentrations below those that block pyramidal neuron NMDARs and LTP in the CA1 region of the hippocampus. Neuropharmacology, 202108846. https://doi.org/10.1016/j.neuropharm.2021.108846
Laha, Kurt, et al. "CPP impairs contextual learning at concentrations below those that block pyramidal neuron NMDARs and LTP in the CA1 region of the hippocampus." Neuropharmacology vol. 202 (2022): 108846. doi: https://doi.org/10.1016/j.neuropharm.2021.108846
Laha K, Zhu M, Gemperline E, Rau V, Li L, Fanselow MS, Lennertz R, Pearce RA. CPP impairs contextual learning at concentrations below those that block pyramidal neuron NMDARs and LTP in the CA1 region of the hippocampus. Neuropharmacology. 2022 Jan 01;202:108846. doi: 10.1016/j.neuropharm.2021.108846. Epub 2021 Oct 20. PMID: 34687710; PMCID: PMC8627488.
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Neuropharmacology. 2022 Jan 01;202:108846. doi: 10.1016/j.neuropharm.2021.108846. Epub 2021 Oct 20.

CPP impairs contextual learning at concentrations below those that block pyramidal neuron NMDARs and LTP in the CA1 region of the hippocampus.

Neuropharmacology

Kurt Laha, Mengwen Zhu, Erin Gemperline, Vinuta Rau, Lingjun Li, Michael S Fanselow, Richard Lennertz, Robert A Pearce

Affiliations

  1. Department of Anesthesiology, University of Wisconsin-Madison, Madison, WI, USA. Electronic address: [email protected].
  2. Department of Anesthesiology, University of Wisconsin-Madison, Madison, WI, USA. Electronic address: [email protected].
  3. Department of Chemistry, University of Wisconsin-Madison, Madison, WI, USA. Electronic address: [email protected].
  4. Department of Anesthesiology, University of California-San Francisco, San Francisco, CA, USA. Electronic address: [email protected].
  5. Department of Chemistry, University of Wisconsin-Madison, Madison, WI, USA; School of Pharmacy, University of Wisconsin-Madison, Madison, WI, USA. Electronic address: [email protected].
  6. Departments of Psychology and Psychiatry, University of California, Los Angeles, Los Angeles, CA, USA. Electronic address: [email protected].
  7. Department of Anesthesiology, University of Wisconsin-Madison, Madison, WI, USA. Electronic address: [email protected].
  8. Department of Anesthesiology, University of Wisconsin-Madison, Madison, WI, USA. Electronic address: [email protected].

PMID: 34687710 PMCID: PMC8627488 DOI: 10.1016/j.neuropharm.2021.108846

Abstract

Drugs that block N-methyl-d-aspartate receptors (NMDARs) suppress hippocampus-dependent memory formation; they also block long-term potentiation (LTP), a cellular model of learning and memory. However, the fractional block that is required to achieve these effects is unknown. Here, we measured the dose-dependent suppression of contextual memory in vivo by systemic administration of the competitive antagonist (R,S)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP); in parallel, we measured the concentration-dependent block by CPP of NMDAR-mediated synapses and LTP of excitatory synapses in hippocampal brain slices in vitro. We found that the dose of CPP that suppresses contextual memory in vivo (EC50 = 2.3 mg/kg) corresponds to a free concentration of 53 nM. Surprisingly, applying this concentration of CPP to hippocampal brain slices had no effect on the NMDAR component of evoked field excitatory postsynaptic potentials (fEPSP

Copyright © 2021 Elsevier Ltd. All rights reserved.

Keywords: (R,S)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid; CPP; Contextual fear conditioning; LTP; Long term potentiation; NMDA receptors

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