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Sex differences in the brain's dopamine signature of cigarette smoking.

ABSTRACT: Cigarette smoking is a major public health danger. Women and men smoke for different reasons and cessation treatments, such as the nicotine patch, are preferentially beneficial to men. The biological substrates of these sex differences are unknown. Earlier PET studies reported conflicting findings but were each hampered by experimental and/or analytical limitations. Our new image analysis technique, lp-ntPET (Normandin et al., 2012; Morris et al., 2013; Kim et al., 2014), has been optimized for capturing brief (lasting only minutes) and highly localized dopaminergic events in dynamic PET data. We coupled our analysis technique with high-resolution brain scanning and high-frequency motion correction to create the optimal experiment for capturing and characterizing the effects of smoking on the mesolimbic dopamine system in humans. Our main finding is that male smokers smoking in the PET scanner activate dopamine in the right ventral striatum during smoking but female smokers do not. This finding-men activating more ventrally than women-is consistent with the established notion that men smoke for the reinforcing drug effect of cigarettes whereas women smoke for other reasons, such as mood regulation and cue reactivity. lp-ntPET analysis produces a novel multidimensional endpoint: voxel-level temporal patterns of neurotransmitter release ("DA movies") in individual subjects. By examining these endpoints quantitatively, we demonstrate that the timing of dopaminergic responses to cigarette smoking differs between men and women. Men respond consistently and rapidly in the ventral striatum whereas women respond faster in a discrete subregion of the dorsal putamen.

SUBMITTER: Cosgrove KP

PROVIDER: S-EPMC4261105 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Sex differences in the brain's dopamine signature of cigarette smoking.

Cosgrove Kelly P KP Wang Shuo S Kim Su-Jin SJ McGovern Erin E Nabulsi Nabeel N Gao Hong H Labaree David D Tagare Hemant D HD Sullivan Jenna M JM Morris Evan D ED

The Journal of neuroscience : the official journal of the Society for Neuroscience 20141201 50

Cigarette smoking is a major public health danger. Women and men smoke for different reasons and cessation treatments, such as the nicotine patch, are preferentially beneficial to men. The biological substrates of these sex differences are unknown. Earlier PET studies reported conflicting findings but were each hampered by experimental and/or analytical limitations. Our new image analysis technique, lp-ntPET (Normandin et al., 2012; Morris et al., 2013; Kim et al., 2014), has been optimized for ...[more]

PMID: 25505336

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Project description:IntroductionWomen have lower rates of quitting than men with both bupropion and nicotine replacement. It is unknown whether varenicline demonstrates differential efficacy for men and women. The purpose of this study was to conduct the first comprehensive meta-analysis of clinical trial data examining sex differences in the efficacy of varenicline for smoking cessation.MethodsSearching MEDLINE, EMBASE, and PsychINFO, 17 of 43 clinical trials of varenicline for smoking cessation published through December 31, 2014 were low-bias randomized double-blind placebo-controlled trials. Data (n = 6710 smokers, 34% female, n = 16 studies, 96% of available data) was analyzed with Metafor program in R. Outcome endpoints were 7-day point-prevalence (PP) and continuous-abstinence (CA) at week 12 (end of treatment), week 24 (6-month follow-up), and week 52 (12-month follow-up).ResultsUsing placebo, women were less likely than men to quit (PP-12, CA-24; P < .05 for sex). Using varenicline, similar rates of abstinence for men and women were demonstrated for all six outcomes (eg, PP-12 abstinence rates were 53% in both women and men). Varenicline versus placebo outcomes demonstrated that varenicline was more effective for women for short and intermediate outcomes (PP-12, CA-12, CA-24; P < .05 sex × medication interaction). For end-of-treatment PP, varenicline was 46% more effective for women. For continuous abstinence, varenicline was 34% (CA-12) and 31% (CA-24) more effective for women.ConclusionsUnlike other smoking cessation medications, varenicline demonstrated greater efficacy among women smokers for short and immediate-term outcomes and equal efficacy for 1-year outcomes. Varenicline may be particularly useful for reducing the sex disparity typically seen in rates of smoking cessation.ImplicationsVarenicline is currently the most effective FDA-approved smoking cessation medication and this is the first demonstration that women compared with men have a preferred therapeutic response for a smoking cessation medication when considering short-term outcomes. Importantly, this is also the first demonstration that women have similar rates of quitting to men when considering longer-term, 1-year outcomes.

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Sex differences in the brain's dopamine signature of cigarette smoking.

Publications

Sex differences in the brain's dopamine signature of cigarette smoking.

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