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Imaging nicotine- and amphetamine-induced dopamine release in rhesus monkeys with [(11)C]PHNO vs [(11)C]raclopride PET.
Neuropsychopharmacology. 2014 Mar; 39(4):866-74.N

Abstract

The radiotracer [(11)C]PHNO may have advantages over other dopamine (DA) D2/D3 receptor ligands because, as an agonist, it measures high-affinity, functionally active D2/D3 receptors, whereas the traditionally used radiotracer [(11)C]raclopride measures both high- and low-affinity receptors. Our aim was to take advantage of the strength of [(11)C]PHNO for measuring the small DA signal induced by nicotine, which has been difficult to measure in preclinical and clinical neuroimaging studies. Nicotine- and amphetamine-induced DA release in non-human primates was measured with [(11)C]PHNO and [(11)C]raclopride positron emission tomography (PET) imaging. Seven adult rhesus monkeys were imaged on a FOCUS 220 PET scanner after injection of a bolus of [(11)C]PHNO or [(11)C]raclopride in three conditions: baseline; preinjection of nicotine (0.1 mg/kg bolus+0.08 mg/kg infusion over 30 min); preinjection of amphetamine (0.4 mg/kg, 5 min before radiotracer injection). DA release was measured as change in binding potential (BPND). Nicotine significantly decreased BPND in the caudate (7 ± 8%), the nucleus accumbens (10 ± 7%), and in the globus pallidus (13 ± 15%) measured with [(11)C]PHNO, but did not significantly decrease BPND in the putamen or the substantia nigra or in any region when measured with [(11)C]raclopride. Amphetamine significantly reduced BPND in all regions with both radiotracers. In the striatum, larger amphetamine-induced changes were detected with [(11)C]PHNO compared with [(11)C]raclopride (52-64% vs 33-35%, respectively). We confirmed that [(11)C]PHNO is more sensitive than [(11)C]raclopride to nicotine- and amphetamine-induced DA release. [(11)C]PHNO PET may be more sensitive to measuring tobacco smoking-induced DA release in human tobacco smokers.

Authors+Show Affiliations

Department of Diagnostic Radiology, Yale PET Center, Yale University School of Medicine, New Haven, CT, USA.Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.Department of Diagnostic Radiology, Yale PET Center, Yale University School of Medicine, New Haven, CT, USA.Department of Diagnostic Radiology, Yale PET Center, Yale University School of Medicine, New Haven, CT, USA.Department of Diagnostic Radiology, Yale PET Center, Yale University School of Medicine, New Haven, CT, USA.Department of Diagnostic Radiology, Yale PET Center, Yale University School of Medicine, New Haven, CT, USA.GlaxoSmithKline, London, UK.GlaxoSmithKline, London, UK.Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.Department of Diagnostic Radiology, Yale PET Center, Yale University School of Medicine, New Haven, CT, USA.1] Department of Diagnostic Radiology, Yale PET Center, Yale University School of Medicine, New Haven, CT, USA [2] Department of Biomedical Engineering, Yale University School of Medicine, New Haven, CT, USA.1] Department of Diagnostic Radiology, Yale PET Center, Yale University School of Medicine, New Haven, CT, USA [2] Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA [3] Department of Biomedical Engineering, Yale University School of Medicine, New Haven, CT, USA.1] Department of Diagnostic Radiology, Yale PET Center, Yale University School of Medicine, New Haven, CT, USA [2] Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

24220025

Citation

Gallezot, Jean-Dominique, et al. "Imaging Nicotine- and Amphetamine-induced Dopamine Release in Rhesus Monkeys With [(11)C]PHNO Vs [(11)C]raclopride PET." Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, vol. 39, no. 4, 2014, pp. 866-74.
Gallezot JD, Kloczynski T, Weinzimmer D, et al. Imaging nicotine- and amphetamine-induced dopamine release in rhesus monkeys with [(11)C]PHNO vs [(11)C]raclopride PET. Neuropsychopharmacology. 2014;39(4):866-74.
Gallezot, J. D., Kloczynski, T., Weinzimmer, D., Labaree, D., Zheng, M. Q., Lim, K., Rabiner, E. A., Ridler, K., Pittman, B., Huang, Y., Carson, R. E., Morris, E. D., & Cosgrove, K. P. (2014). Imaging nicotine- and amphetamine-induced dopamine release in rhesus monkeys with [(11)C]PHNO vs [(11)C]raclopride PET. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, 39(4), 866-74. https://doi.org/10.1038/npp.2013.286
Gallezot JD, et al. Imaging Nicotine- and Amphetamine-induced Dopamine Release in Rhesus Monkeys With [(11)C]PHNO Vs [(11)C]raclopride PET. Neuropsychopharmacology. 2014;39(4):866-74. PubMed PMID: 24220025.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Imaging nicotine- and amphetamine-induced dopamine release in rhesus monkeys with [(11)C]PHNO vs [(11)C]raclopride PET. AU - Gallezot,Jean-Dominique, AU - Kloczynski,Tracy, AU - Weinzimmer,David, AU - Labaree,David, AU - Zheng,Ming-Qiang, AU - Lim,Keunpoong, AU - Rabiner,Eugenii A, AU - Ridler,Khanum, AU - Pittman,Brian, AU - Huang,Yiyun, AU - Carson,Richard E, AU - Morris,Evan D, AU - Cosgrove,Kelly P, Y1 - 2013/10/15/ PY - 2013/02/12/received PY - 2013/07/15/revised PY - 2013/07/16/accepted PY - 2013/11/14/entrez PY - 2013/11/14/pubmed PY - 2014/10/11/medline SP - 866 EP - 74 JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JO - Neuropsychopharmacology VL - 39 IS - 4 N2 - The radiotracer [(11)C]PHNO may have advantages over other dopamine (DA) D2/D3 receptor ligands because, as an agonist, it measures high-affinity, functionally active D2/D3 receptors, whereas the traditionally used radiotracer [(11)C]raclopride measures both high- and low-affinity receptors. Our aim was to take advantage of the strength of [(11)C]PHNO for measuring the small DA signal induced by nicotine, which has been difficult to measure in preclinical and clinical neuroimaging studies. Nicotine- and amphetamine-induced DA release in non-human primates was measured with [(11)C]PHNO and [(11)C]raclopride positron emission tomography (PET) imaging. Seven adult rhesus monkeys were imaged on a FOCUS 220 PET scanner after injection of a bolus of [(11)C]PHNO or [(11)C]raclopride in three conditions: baseline; preinjection of nicotine (0.1 mg/kg bolus+0.08 mg/kg infusion over 30 min); preinjection of amphetamine (0.4 mg/kg, 5 min before radiotracer injection). DA release was measured as change in binding potential (BPND). Nicotine significantly decreased BPND in the caudate (7 ± 8%), the nucleus accumbens (10 ± 7%), and in the globus pallidus (13 ± 15%) measured with [(11)C]PHNO, but did not significantly decrease BPND in the putamen or the substantia nigra or in any region when measured with [(11)C]raclopride. Amphetamine significantly reduced BPND in all regions with both radiotracers. In the striatum, larger amphetamine-induced changes were detected with [(11)C]PHNO compared with [(11)C]raclopride (52-64% vs 33-35%, respectively). We confirmed that [(11)C]PHNO is more sensitive than [(11)C]raclopride to nicotine- and amphetamine-induced DA release. [(11)C]PHNO PET may be more sensitive to measuring tobacco smoking-induced DA release in human tobacco smokers. SN - 1740-634X UR - https://www.unboundmedicine.com/medline/citation/24220025/Imaging_nicotine__and_amphetamine_induced_dopamine_release_in_rhesus_monkeys_with_[_11_C]PHNO_vs_[_11_C]raclopride_PET_ L2 - https://doi.org/10.1038/npp.2013.286 DB - PRIME DP - Unbound Medicine ER -