title: Sex-specific differences in GABA(A) -benzodiazepine receptor availability: relationship with sensitivity to pain and tobacco smoking craving.
abstract: Sex differences exist in tobacco smoking behaviors. Nicotine, the primary addictive ingredient in tobacco smoke, indirectly affects γ-amino butyric acid (GABA) function. Previous studies reported sex-by-smoking interactions in brain GABA levels. The goal of the present study was to evaluate if there is a sex-by-smoking interaction at the GABA(A)-benzodiazepine receptors (GABA(A)-BZRs), as well as relationships between GABA(A)-BZR availability and behavioral variables before and after 1 week of smoking cessation. Twenty-six women (8 non-smokers, age 36.0 ± 13.4 years; 19 smokers, age 34.6 ± 8.9 years) and 25 men (8 non-smokers, age 37.9 ± 13.8 years; 17 smokers, 34.1 ± 12.4 years) were imaged using [123I]iomazenil and single-photon emission computed tomography. Smokers were imaged at baseline 7 hours after the last cigarette. A significantly great number of men were able to abstain from smoking for 1 week (P = 0.003). There were no significant differences in nicotine dependence and cigarette craving, mood or pain sensitivity between male and female smokers. There was a significant effect of gender across all brain regions (frontal, parietal, anterior cingulate, temporal and occipital cortices, and cerebellum; P < 0.05), with all women (smokers and non-smokers combined) having a higher GABA(A)-BZR availability than all men. There was a negative correlation between GABA(A)-BZR availability and craving (P ≤ 0.02) and pain sensitivity (P = 0.04) in female smokers but not male smokers. This study provides further evidence of a sex-specific regulation of GABA(A)-BZR availability in humans and demonstrates the potential for GABA(A)-BZRs to mediate tobacco smoking craving and pain symptoms differentially in female and male smokers.
authors.affiliation: Department of Psychiatry, Yale University and the VACHS, West Haven, CT 06516, USA. irina.esterlis@yale.edu
authors.forename: Irina
authors.initials: I
authors.lastname: Esterlis
authors.forename: Sherry A
authors.initials: SA
authors.lastname: McKee
authors.forename: Kathryne
authors.initials: K
authors.lastname: Kirk
authors.forename: Dianne
authors.initials: D
authors.lastname: Lee
authors.forename: Frederic
authors.initials: F
authors.lastname: Bois
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Stiklus
authors.forename: John P
authors.initials: JP
authors.lastname: Seibyl
authors.forename: Suchitra
authors.initials: S
authors.lastname: Krishnan-Sarin
authors.forename: Stephanie S
authors.initials: SS
authors.lastname: O'Malley
authors.forename: Julie K
authors.initials: JK
authors.lastname: Staley
authors.forename: Kelly P
authors.initials: KP
authors.lastname: Cosgrove
mesh_terms: D000328:Adult; D000342:Affective Symptoms / Q000523:psychology; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005442:Flumazenil / Q000031:analogs & derivatives; D018757:GABA Modulators; D006801:Humans; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000494:pharmacology; D058748:Pain Perception / Q000187:drug effects / Q000502:physiology*; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D012727:Sex Characteristics; D016540:Smoking Cessation; D013375:Substance Withdrawal Syndrome / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D014029:Tobacco Use Disorder / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D055815:Young Adult
chemical_list: D018757:GABA Modulators; D011963:Receptors, GABA-A; D005442:Flumazenil; D009538:Nicotine; C063038:iomazenil