title: Long-lasting occupancy of central nicotinic acetylcholine receptors after smoking: a PET study in monkeys.
abstract: The aim of this study was to compare the degree of occupancy of central nicotinic acetylcholine receptors (nAChR) in isoflurane anaesthetized baboon brain following inhalation of tobacco smoke (one cigarette containing 0.9 mg nicotine) or i.v. nicotine (0.6 mg i.v.). [18F]Fluoro-A-85380 and positron emission tomography (PET) were used to assess the distribution volumes (DV) of the radiotracer in selected brain areas using a one-compartment model. Eighty minutes after nicotine i.v., DV was reduced by 50 and 66% in the thalamus and putamen, respectively. Six hours after nicotine, a reduction in DV (27% in the thalamus) was still observed. Eighty minutes after inhalation of tobacco smoke, DV was decreased by 52 and 65% in the thalamus and putamen, respectively. Previous PET experiments have demonstrated a short-lasting interaction of [11C]nicotine with nAChRs. Thus, we hypothesized that a metabolite of nicotine with high affinity and long half-live (several hours) could bind at nAChRs. Eighty minutes after a high dose of nornicotine (0.5 mg i.v.), DV was reduced by 53 and 31% in thalamus and putamen, respectively. No significant effect was observed following 0.15 mg nornicotine. Therefore, nornicotine could contribute to the long-lasting occupancy of central nAChRs after smoking.
authors.affiliation: Service Hospitalier Frédéric Joliot, DRM-DSV-CEA, Orsay, France. valette@shfj.cea.fr
authors.forename: Héric
authors.initials: H
authors.lastname: Valette
authors.forename: Michel
authors.initials: M
authors.lastname: Bottlaender
authors.forename: Frédéric
authors.initials: F
authors.lastname: Dollé
authors.forename: Christine
authors.initials: C
authors.lastname: Coulon
authors.forename: Michèle
authors.initials: M
authors.lastname: Ottaviani
authors.forename: André
authors.initials: A
authors.lastname: Syrota
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D007275:Injections, Intravenous; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology; D010215:Papio; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012016:Reference Values; D012907:Smoking; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
chemical_list: D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D009538:Nicotine; C005311:nornicotine