PET imaging of acetylcholinesterase inhibitor-induced effects on α4β2 nicotinic acetylcholine receptor binding
Article first published online: 30 AUG 2013
Copyright © 2013 Wiley Periodicals, Inc.
Volume 67, Issue 12, pages 882–886, December 2013
How to Cite
Hillmer, A. T., Wooten, D. W., Farhoud, M., Higgins, A. T., Lao, P. J., Barnhart, T. E., Mukherjee, J. and Christian, B. T. (2013), PET imaging of acetylcholinesterase inhibitor-induced effects on α4β2 nicotinic acetylcholine receptor binding. Synapse, 67: 882–886. doi: 10.1002/syn.21698
- Issue published online: 15 OCT 2013
- Article first published online: 30 AUG 2013
- Accepted manuscript online: 1 AUG 2013 10:19AM EST
- Manuscript Accepted: 19 JUL 2013
- Manuscript Revised: 20 JUN 2013
- Manuscript Received: 17 MAY 2013
- NIH. Grant Numbers: MH086014, T32CA009206
- nicotinic acetylcholine receptor;
- acetylcholinesterase inhibitors;
Acetylcholinesterase inhibitors (AChEIs) are drugs that increase synaptic acetylcholine (ACh) concentrations and are under investigation as treatments for symptoms accompanying Alzheimer's disease. The goal of this work was to use PET imaging to evaluate alterations of in vivo α4β2 nicotinic acetylcholine receptor (nAChR) binding induced by the AChEIs physostigmine (PHY) and galanthamine (GAL). The α4β2 nAChR-specific radioligand [18F]nifene was used to examine the effects of 0.1–0.2 mg/kg PHY, 5 mg/kg GAL, and saline in three separate experiments all performed on each of two rat subjects. A 60-min bolus-infusion protocol was used with drug administered after 30 min. Data from the thalamus and cortex were analyzed with a graphical model accounting for neurotransmitter activation using the cerebellum as a reference region to test for transient competition with bound [18F]nifene. Significant [18F]nifene displacement was detected in both regions during one PHY and both GAL studies, while no significant competition was observed in both saline studies. This preliminary work indicates the viability of [18F]nifene in detecting increases in synaptic ACh induced by AChEIs. Synapse 67:882–886, 2013. © 2013 Wiley Periodicals, Inc.