title: Up-regulation of nicotinic acetylcholine receptors in menthol cigarette smokers.
abstract: One-third of smokers primarily use menthol cigarettes and usage of these cigarettes leads to elevated serum nicotine levels and more difficulty quitting in standard treatment programmes. Previous brain imaging studies demonstrate that smoking (without regard to cigarette type) leads to up-regulation of β(2)*-containing nicotinic acetylcholine receptors (nAChRs). We sought to determine if menthol cigarette usage results in greater nAChR up-regulation than non-menthol cigarette usage. Altogether, 114 participants (22 menthol cigarette smokers, 41 non-menthol cigarette smokers and 51 non-smokers) underwent positron emission tomography scanning using the α(4)β(2)* nAChR radioligand 2-[(18)F]fluoro-A-85380 (2-FA). In comparing menthol to non-menthol cigarette smokers, an overall test of 2-FA total volume of distribution values revealed a significant between-group difference, resulting from menthol smokers having 9-28% higher α(4)β(2)* nAChR densities than non-menthol smokers across regions. In comparing the entire group of smokers to non-smokers, an overall test revealed a significant between-group difference, resulting from smokers having higher α(4)β(2)* nAChR levels in all regions studied (36-42%) other than thalamus (3%). Study results demonstrate that menthol smokers have greater up-regulation of nAChRs than non-menthol smokers. This difference is presumably related to higher nicotine exposure in menthol smokers, although other mechanisms for menthol influencing receptor density are possible. These results provide additional information about the severity of menthol cigarette use and may help explain why these smokers have more trouble quitting in standard treatment programmes.
authors.affiliation: Department of Psychiatry, University of California at Los Angeles, Los Angeles, USA. abrody@ucla.edu
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Brody
authors.forename: Alexey G
authors.initials: AG
authors.lastname: Mukhin
authors.forename: Jaime
authors.initials: J
authors.lastname: La Charite
authors.forename: Karen
authors.initials: K
authors.lastname: Ta
authors.forename: Judah
authors.initials: J
authors.lastname: Farahi
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Sugar
authors.forename: Michael S
authors.initials: MS
authors.lastname: Mamoun
authors.forename: Evan
authors.initials: E
authors.lastname: Vellios
authors.forename: Meena
authors.initials: M
authors.lastname: Archie
authors.forename: Maggie
authors.initials: M
authors.lastname: Kozman
authors.forename: Jonathan
authors.initials: J
authors.lastname: Phuong
authors.forename: Franca
authors.initials: F
authors.lastname: Arlorio
authors.forename: Mark A
authors.initials: MA
authors.lastname: Mandelkern
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001384:Azetidines / Q000494:pharmacology; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects; D001931:Brain Mapping; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D008297:Male; D008610:Menthol / Q000008:administration & dosage*; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012907:Smoking / Q000097:blood* / Q000473:pathology*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: C104288:A 85380; D001384:Azetidines; D005462:Fluorine Radioisotopes; D011978:Receptors, Nicotinic; D008610:Menthol