Abstract
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Objectives The goal of this work was to examine the interactions of lobeline, an α4β2* nicotinic acetylcholine receptor (nAChR) antagonist and amine blood-brain barrier (BBB) amine transporter inhibitor, with the in vivo kinetics of 18F-nifene using PET imaging in the rat brain.
Methods The interactions of lobeline and 18F-nifene were investigated through two separate PET imaging sessions, each conducted on two rat subjects. First, competition at the α4β2* nAChR site was directly examined by administering displacement and blockade doses of 1 mg/kg lobeline (i.v.) between two 18F-nifene injections. Potential inhibition of the BBB amine transporter was investigated with the second experiment consisting of three 18F-nifene injections, one at baseline, the second following blocking of specific binding with 0.3 mg/kg (-)nicotine (i.v.), and finally following 1 mg/kg lobeline.
Results 18F-Nifene was rapidly displaced by lobeline in the densely α4β2* populated thalamus. In the absence of specific binding, slight decreases in transport rates of 18F-nifene from plasma to tissue were observed following lobeline administration. These alterations may be due to inhibition of the BBB amine transporter or reductions in blood flow caused by lobeline. Significant displacement of 18F-nifene was observed in the cerebellum, suggesting the presence of specific binding in this region in rats.
Conclusions Lobeline exhibits pronounced competition with 18F-nifene at the α4β2* nAChR site, however, only a small effect of indeterminate physiological origin was observed in transport of radioligand across the BBB at a 1 mg/kg dose.
Research Support MH086014