The Effects of Lobeline on α4β2* Nicotinic Acetylcholine Receptor Binding and Uptake of [(18)F]Nifene in Rats.

Department of Medical Physics, University of Wisconsin-Madison, Madison, WI, 1111 Highland Ave, Room 1005, Madison, WI 53705
Journal of Neuroscience Methods (Impact Factor: 2.05). 01/2013; 214(2). DOI: 10.1016/j.jneumeth.2013.01.018
Source: PubMed


Lobeline is a potential smoking cessation drug with affinity for the α4β2 nicotinic acetylcholine receptor and may inhibit the blood-brain barrier (BBB) amine transporter. The goal of this work was to use PET imaging to evaluate the effects of lobeline on the kinetic properties of [(18)F]nifene in the rat brain.

Direct α4β2* competition of lobeline with [(18)F]nifene was evaluated using imaging experiments with both displacing and blocking doses of lobeline (1mg/kg, i.v.) given between two injections of [(18)F]nifene separated by 50min. Inhibition of the BBB amine transporter was examined using a separate imaging protocol with three injections of [(18)F]nifene, first at baseline, then following (-)nicotine blocking, and finally following lobeline blocking.

Rapid displacement of [(18)F]nifene was observed in the α4β2*-rich thalamus following lobeline administration, suggesting direct competition of the drug at α4β2* sites. Slight decreases in BBB transport of [(18)F]nifene were observed when the α4β2* system was first saturated with (-)nicotine and then given lobeline. This perturbation may be due to inhibition of the BBB amine transporter by lobeline or reductions in blood flow. Significant cerebellar displacement of [(18)F]nifene was found following the administration of both lobeline and (-)nicotine, indicating detectable specific binding in the rat cerebellum.

The competition of lobeline with [(18)F]nifene is largely dominated at the α4β2* binding site and only small perturbations in BBB transport of [(18)F]nifene are seen at the 1mg/kg dose. Similar experiments could be used to study other drugs as therapeutic agents for smoking cessation with PET.

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Available from: Jogeshwar Mukherjee, Dec 02, 2014
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