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Biol Psychiatry. 2015 Feb 1;77(3):266-75. doi: 10.1016/j.biopsych.2014.06.024. Epub 2014 Jul 10.

In vivo ketamine-induced changes in [¹¹C]ABP688 binding to metabotropic glutamate receptor subtype 5.

Author information

1
Departments of Psychiatry, Stony Brook University, Stony Brook, New York, New York; Applied Mathematics and Statistics, Stony Brook University, Stony Brook, New York, New York. Electronic address: Christine.DeLorenzo@stonybrookmedicine.edu.
2
Department of Psychiatry, Columbia University, New York, New York.
3
Department of Psychiatry, Columbia University, New York, New York; Departments of Biomedical Engineering, Yale University, New Haven; Child Study Center, Yale University, New Haven.
4
Departments of Psychiatry, Yale University, New Haven.
5
Department of Psychiatry, Columbia University, New York, New York; Departments of Biomedical Engineering, Yale University, New Haven; Clinical Neuroscience Division, National Center for PTSD, West Haven, Connecticut.
6
Departments of Radiology, Stony Brook University, Stony Brook, New York, New York.
7
Departments of Preventive Medicine, Stony Brook University, Stony Brook, New York, New York.
8
Applied Mathematics and Statistics, Stony Brook University, Stony Brook, New York, New York.
9
Departments of Biomedical Engineering, Stony Brook University, Stony Brook, New York, New York.
10
Departments of Psychiatry, Yale University, New Haven; Diagnostic Radiology, Yale University, New Haven.

Abstract

BACKGROUND:

At subanesthetic doses, ketamine, an N-methyl-D-aspartate glutamate receptor antagonist, increases glutamate release. We imaged the acute effect of ketamine on brain metabotropic glutamatergic receptor subtype 5 with a high-affinity positron emission tomography (PET) ligand [(11)C]ABP688 (E)-3-[2-(6-methyl-2-pyridinyl)ethynyl]-2-cyclohexen-1-one-O-(methyl-11C)oxime, a negative allosteric modulator of the metabotropic glutamatergic receptor subtype 5.

METHODS:

Two [(11)C]ABP688 PET scans were performed in 10 healthy nonsmoking human volunteers (34 ± 13 years old); the two PET scans were performed on the same day-before (scan 1) and during intravenous ketamine administration (.23 mg/kg over 1 min, then .58 mg/kg over 1 hour; scan 2). The PET data were acquired for 90 min immediately after [(11)C]ABP688 bolus injection. Input functions were obtained through arterial blood sampling with metabolite analysis.

RESULTS:

A significant reduction in [(11)C]ABP688 volume of distribution was observed in scan 2 relative to scan 1 of 21.3% ± 21.4%, on average, in the anterior cingulate, medial prefrontal cortex, orbital prefrontal cortex, ventral striatum, parietal lobe, dorsal putamen, dorsal caudate, amygdala, and hippocampus. There was a significant increase in measurements of dissociative state after ketamine initiation (p < .05), which resolved after completion of the scan.

CONCLUSIONS:

This study provides first evidence that ketamine administration decreases [(11)C]ABP688 binding in vivo in human subjects. The results suggest that [(11)C]ABP688 binding is sensitive to ketamine-induced effects, although the high individual variation in ketamine response requires further examination.

KEYWORDS:

Brain; Glutamate; Ketamine; PET; [(11)C]ABP688; mGluR5

PMID:
25156701
PMCID:
PMC4277907
DOI:
10.1016/j.biopsych.2014.06.024
[Indexed for MEDLINE]
Free PMC Article
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