Transdermal nicotine patch (TNP) is 1 of the most commonly used smoking cessation treatments; however, the efficacy of TNP by sex is not yet clear. The purpose of the current review was to synthesize how sex has been considered in published clinical trials of TNP for smoking cessation. The specific aims of the study were to examine the inclusion of sex in analyses of cessation outcomes, TNP-related variables (compliance, side effects), and quit- related variables (withdrawal, cravings); to review the consideration of sex-related variables (menstrual cycle phase, pregnancy); and to identify needs for future research. Potential articles published through December 31, 2013 were identified through a MEDLINE search of the terms "clinical trial," "nicotine patch," and "smoking cessation." Forty-two studies used all 3 terms and met the inclusion criteria. Approximately half of the studies reported that they considered sex in smoking cessation outcomes, with 15 studies finding no difference by sex and 7 studies finding better outcomes for men versus women. Only 5 studies reported data on outcomes by sex in their publications. No studies reported analysis of TNP compliance or withdrawal by sex. In the 1 study that examined side effects by sex, more women than men reported discontinuing TNP because of skin irritation. No study examined the association of cessation outcomes with menstrual cycle phase. There is a need to include sex in research on TNP, as well as other pharmacological and behavioral smoking treatments, to clarify the picture of treatment efficacy for women compared with men. (PsycINFO Database Record (c) 2014 APA, all rights reserved).
[Show abstract][Hide abstract] ABSTRACT: The a2A-noradrenergic agonist guanfacine can decreases stress-induced smoking in female, but not male, human smokers. It is not known whether these effects are due to effects on mood regulation and/or result from nicotinic-cholinergic interactions.
The objective of the study was to determine whether there are sex differences in the effect of guanfacine in tests of anxiolytic and antidepressant efficacy in mice at baseline and in a hypercholinergic model of depression induced by the acetylcholinesterase inhibitor physostigmine.
The effects of guanfacine were measured in the light/dark box, tail suspension, and the forced swim test in female and male C57BL/6J mice. In parallel, electrophysiological properties were evaluated in the prefrontal cortex, a critical brain region involved in stress responses. c-fos immunoreactivity was measured in other brain regions known to regulate mood.
Despite a baseline sex difference in behavior in the forced swim test (female mice were more immobile), guanfacine had similar, dose-dependent, antidepressant-like effects in mice of both sexes (optimal dose, 0.15 mg/kg). An antidepressant-like effect of guanfacine was also observed following pre-treatment with physostigmine. A sex difference in the paired-pulse ratio in the prefrontal cortex (PFC) (male, 1.4; female, 2.1) was observed at baseline that was normalized by guanfacine. Other brain areas involved in cholinergic control of depression-like behaviors, including the basolateral amygdala and lateral septum, showed sex-specific changes in c-fos expression.
Guanfacine has a robust antidepressant-like effect and can reverse a depression-like state induced by increased acetylcholine (ACh) signaling. These data suggest that different brain areas are recruited in female and male mice, despite similar behavioral responses to guanfacine.
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