title: 123I-5-IA-85380 SPECT imaging of nicotinic acetylcholine receptor availability in nonsmokers: effects of sex and menstrual phase.
abstract: The study of the effects of sex and hormones on brain chemistry and neurotransmission is of increasing importance as evidence emerges of sex differences in behavioral symptoms and treatment response in neuropsychiatric disorders. The nicotinic acetylcholine receptor (nAChR) system has been implicated in a variety of psychiatric disorders, including tobacco smoking, for which there is strong evidence supporting sex differences in behaviors and response to smoking cessation treatments. We examined the availability of nAChR containing the beta(2) subunit in healthy men and women and the influence of menstrual phase among women.
  
  
  METHODS
  Ten men and 19 women nonsmokers underwent one (123)I-5-IA-85380 ((123)I-5-IA) SPECT scan and one MRI scan. A subset of 9 women, aged 18-39 y, underwent a second (123)I-5-IA scan. These 9 women were scanned during the early follicular (days 4-7 in 8 subjects and day 11 in 1 subject) and mid-luteal (days 19-25) phases of their menstrual cycle. Hormone levels were measured in all women to confirm the phase of the cycle.
  
  
  RESULTS
  Regional brain activity (kBq/cm(3)) was higher (39%-54%) in women than in men nonsmokers. When regional brain activity was normalized to total plasma parent to correct for individual differences in radiotracer metabolism (V(T)'), differences of 10%-16% were observed, with women greater than men. In contrast, when regional brain activity was normalized to free plasma parent (V(T)), there was less than a 4% difference by sex in regional brain beta(2)-nAChR availability. These sex differences in kBq/cm(3) and V(T)' resulted from significantly higher levels of total plasma parent, free fraction (f(1)), and free plasma parent in women than in men nonsmokers. No differences in plasma measures or brain beta(2)-nAChR availability were observed across the menstrual cycle for any outcome measure.
  
  
  CONCLUSIONS
  Overall, these findings demonstrate no significant difference in brain beta(2)-nAChR availability between men and women nonsmokers or across the menstrual cycle. Importantly, these findings demonstrate sex differences in radiotracer metabolism and plasma protein binding and highlight the critical need to measure plasma radiotracer levels and f(1) in studies that include both sexes.
authors.affiliation: Yale University School of Medicine, New Haven, Connecticut, USA. kelly.cosgrove@yale.edu
authors.forename: Kelly P
authors.initials: KP
authors.lastname: Cosgrove
authors.forename: Effie M
authors.initials: EM
authors.lastname: Mitsis
authors.forename: Frederic
authors.initials: F
authors.lastname: Bois
authors.forename: Erin
authors.initials: E
authors.lastname: Frohlich
authors.forename: Gilles D
authors.initials: GD
authors.lastname: Tamagnan
authors.forename: Erica
authors.initials: E
authors.lastname: Krantzler
authors.forename: Edward
authors.initials: E
authors.lastname: Perry
authors.forename: Paul K
authors.initials: PK
authors.lastname: Maciejewski
authors.forename: C Neill
authors.initials: CN
authors.lastname: Epperson
authors.forename: Sharon
authors.initials: S
authors.lastname: Allen
authors.forename: Stephanie
authors.initials: S
authors.lastname: O'malley
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Mazure
authors.forename: John P
authors.initials: JP
authors.lastname: Seibyl
authors.forename: Christopher H
authors.initials: CH
authors.lastname: van Dyck
authors.forename: Julie K
authors.initials: JK
authors.lastname: Staley
mesh_terms: D000328:Adult; D001384:Azetidines / Q000493:pharmacokinetics*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008597:Menstrual Cycle / Q000378:metabolism*; D011725:Pyridines / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012737:Sex Factors; D012907:Smoking / Q000378:metabolism*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D001384:Azetidines; D011725:Pyridines; D019275:Radiopharmaceuticals; D011978:Receptors, Nicotinic; C426745:5-iodo-3-(2-azetidinylmethoxy)pyridine