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NMDA receptor ion channel activation detected in vivo with [¹⁸F]GE-179 PET after electrical stimulation of rat hippocampus

Lookup NU author(s): Professor David BrooksORCiD

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This is the authors' accepted manuscript of an article that has been published in its final definitive form by Sage Publications Ltd, 2021.

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Abstract

The positron emission tomography (PET) tracer [¹⁸F]GE-179 binds to the phencyclidine (PCP) site in the open N-methyl-D-aspartate receptor ion channel (NMDAR-IC). To demonstrate that PET can visualize increased [¹⁸F]GE-179 uptake by active NMDAR-ICs and that this can be blocked by the PCP antagonist S-ketamine, 15 rats had an electrode unilaterally implanted in their ventral hippocampus. Seven rats had no stimulation, five received pulsed 400 µA supra-threshold 60 Hz stimulation alone, and three received intravenous S-ketamine injection prior to stimulation. Six other rats were not implanted. Each rat had a 90 min [¹⁸F]GE-179 PET scan. Stimulated rats had simultaneous depth-EEG recordings of induced seizure activity. [¹⁸F]GE-179 uptake (volume of distribution, V_T) was compared between hemispheres and between groups. Electrical stimulation induced a significant increase in [¹⁸F]GE-179 uptake at the electrode site compared to the contralateral hippocampus (mean 22% increase in V_T, p=0.0014) and to non-stimulated comparator groups. Rats injected with S-ketamine prior to stimulation maintained non-stimulated levels of [¹⁸F]GE-179 uptake during stimulation. In conclusion, PET visualization of focal [¹⁸F]GE-179 uptake during electrically activated NMDAR-ICs and the demonstration of specificity for PCP sites by blockade with S-ketamine support the in vivo utility of [¹⁸F]GE-179 PET as a use-dependent marker of NMDAR-IC activation.

Publication metadata

Author(s): Vibholm AK, Landau AM, Møller A, Jacobsen J, Vang K, Munk OL, Orlowski D, Sørensen JCH, Brooks DJ

Publication type: Article

Publication status: Published

Journal: Journal of Cerebral Blood Flow and Metabolism

Year: 2021

Volume: 41

Issue: 6

Pages: 1301-1312

Print publication date: 01/06/2021

Online publication date: 22/09/2020

Acceptance date: 03/08/2020

Date deposited: 04/08/2020

ISSN (print): 0271-678X

ISSN (electronic): 1559-7016

Publisher: Sage Publications Ltd

URL: https://doi.org/10.1177/0271678X20954928

DOI: 10.1177/0271678X20954928

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