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- Title
Imaging Nicotine- and Amphetamine-Induced Dopamine Release in Rhesus Monkeys with [<sup>11</sup>C]PHNO vs [<sup>11</sup>C]raclopride PET.
- Authors
Gallezot, Jean-Dominique; Kloczynski, Tracy; Weinzimmer, David; Labaree, David; Zheng, Ming-Qiang; Lim, Keunpoong; Rabiner, Eugenii A; Ridler, Khanum; Pittman, Brian; Huang, Yiyun; Carson, Richard E; Morris, Evan D; Cosgrove, Kelly P
- Abstract
The radiotracer [11C]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 [11C]raclopride measures both high- and low-affinity receptors. Our aim was to take advantage of the strength of [11C]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 [11C]PHNO and [11C]raclopride positron emission tomography (PET) imaging. Seven adult rhesus monkeys were imaged on a FOCUS 220 PET scanner after injection of a bolus of [11C]PHNO or [11C]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 [11C]PHNO, but did not significantly decrease BPND in the putamen or the substantia nigra or in any region when measured with [11C]raclopride. Amphetamine significantly reduced BPND in all regions with both radiotracers. In the striatum, larger amphetamine-induced changes were detected with [11C]PHNO compared with [11C]raclopride (52-64% vs 33-35%, respectively). We confirmed that [11C]PHNO is more sensitive than [11C]raclopride to nicotine- and amphetamine-induced DA release. [11C]PHNO PET may be more sensitive to measuring tobacco smoking-induced DA release in human tobacco smokers.
- Publication
Neuropsychopharmacology, 2014, Vol 39, Issue 4, p866
- ISSN
0893-133X
- Publication type
Academic Journal
- DOI
10.1038/npp.2013.286