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Acute S-ketamine application does not alter cerebral [18F]altanserin binding: a pilot PET study in humans

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Summary

Modeling short-term psychotic states with subanaesthetic doses of ketamine provides substantial experimental evidence in support of the glutamate hypothesis of schizophrenia. Ketamine exerts its pharmacological effects both directly via interactions with glutamate receptors and indirectly by stimulating presynaptic release of endogenous serotonin (5-HT). The aim of this feasibility study was to examine whether acute ketamine-induced 5-HT release interferes with the binding of the 5-HT2A receptor (5-HT2AR) radioligand [18F]altanserin and positron emission tomography (PET). Two subjects treated with ketamine and one subject treated with placebo underwent [18F]altanserin PET at distribution equilibrium conditions. Robust physiological, psychopathological and cognitive effects were present at ketamine plasma concentrations exceeding 100 µg/l during >70 min. Notwithstanding, we observed stable radioligand binding (changes ±95% CI of −1.0 ± 1.6% and +4.1 ± 1.8% versus −1.2 ± 2.6%) in large cortical regions presenting high basal uptake of both, [18F]altanserin and ketamine. Marginal decreases of 4% of radioligand binding were observed in the frontal lobe, and 8% in a posteriorily specified frontomesial subregion. This finding is not compatible with a specific radioligand displacement from 5-HT2AR which should occur proportionally throughout the whole brain. Instead, the spatial pattern of these minor reductions was congruent with ketamine-induced increases in cerebral blood flow observed in a previous study using [15O]butanol PET. This may caused by accelerated clearance of unspecifically bound [18F]altanserin from cerebral tissue with increased perfusion. In conclusion, this study suggests that [18F]altanserin PET is not sensitive to acute neurotransmitter fluctuations under ketamine. Advantageously, the stability of [18F]altanserin PET towards acute influences is a prerequisite for its future use to detect sub-acute and chronic effects of ketamine.

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  1. Institute of Medicine and Brain Imaging Center West, Research Center Juelich, Juelich, Germany

    A. Matusch, R. Hurlemann, E. Rota Kops, O. H. Winz, D. Elmenhorst, H. Herzog, K. Zilles & A. Bauer

  2. Department of Psychiatry, University of Bonn, Bonn, Germany

    R. Hurlemann

  3. C. & O. Vogt Institute for Brain Research, University of Duesseldorf, Duesseldorf, Germany

    K. Zilles

  4. Department of Neurology, University of Duesseldorf, Duesseldorf, Germany

    A. Bauer

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Matusch, A., Hurlemann, R., Rota Kops, E. et al. Acute S-ketamine application does not alter cerebral [18F]altanserin binding: a pilot PET study in humans. J Neural Transm 114, 1433–1442 (2007). https://doi.org/10.1007/s00702-007-0751-3

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