Project IV: Gender, Sex Hormones and Stress-related Smoking (Saladin &Gray) Even with the use of evidence-based treatments, most smokers are unsuccessful when attempting to quit, and cessation rates are particulariy discouraging among women. Gender and sex hormone influences on the relationships between stress, craving, and smoking behavior may be key factors underiying this important health disparity. Recent laboratory findings support this assertion, but further work is needed to (a) measure and characterize the relationship between gender/sex hormones and craving experienced by female and male smokers in their "real worid" (i.e., non-laboratory) environment, (b) examine the relationship between gender/sex hormones and stress-induced changes in smoking behavior, and (c) examine the treatment potential of a novel pharmacological agent (oxytocin) that may address gender-relevant stress-responsive smoking behaviors. A mixed naturalistic and laboratory research strategy is proposed to address current gaps in knowledge. Over a two-week period, female and male smokers will provide daily saliva samples for measurement of sex hormones, and will ufilize a newly developed and validated software implemented on a personal digital assistant (iPhone) to provide real-fime responses to smoking-related and neutral picture cues presented mulfiple times daily in their day-to-day natural environment. Participants will then take part in a laboratory session that will examine the effects of oxytocin on stress reactivity and smoking behavior. Prior to the session, participants will abstain from smoking for 12 hours and provide a salivary sample for measurement of stress/sex hormones (Cortisol, estradiol, progesterone, testosterone) levels. Next, participants will receive either oxytocin or placebo and then be exposed to the Trier Social Stress Test (TSST). Measures collected at mulfiple fime points during the laboratory session will include: craving, stress, negative emofion, heart rate, blood pressure, skin conductance, and Cortisol. Afterthe TSST, participants will complete a smoking resistance task (SRT) in which they will receive a monetary reward for every 5-min period they resist smoking. After the SRT, participants will be allowed to smoke freely during a 1-hour ad libitum smoking period (ASP), with smoking topography assessed via a portable device. It is expected that, in "real worid" setfings, females will be more reacfive to smoking-related cues than male smokers, and that, among females, the ratio of estradiol to progesterone will be positively related to craving. In the laboratory, it is predicted that (a) females will evidence greater stress, craving, and smoking behavior, but less neuroendocrine (Cortisol) reactivity, to the TSST, and (b) oxytocin vs. placebo, will attenuate stress, craving, and Cortisol response to the TSST. Findings from the proposed study will substantially address a key gender-related health disparity, potenfially informing the development of gender-speciflc intervenfions to enhance female smokers'response to cessation treatments. Therefore, the knowledge to be gained may yield signiflcant public health benefits.

Public Health Relevance

Cigarette smoking is arguably the single greatest preventable cause of morbidity and mortality. Importanfiy, women appear to have more difficulty quitting smoking than men. In an effort to increase understanding of this signiflcant health disparity, the proposed study will employ novel and established research methods to examine the (a) role of sex hormones in craving/stress factors that affect the smoking behavior of women and men, and (b) treatment potenfial of a new medicafion.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Specialized Center (P50)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-EMNR-Q (50))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Medical University of South Carolina
United States
Zip Code
Moran-Santa Maria, Megan M; Hartwell, Karen J; Hanlon, Colleen A et al. (2015) Right anterior insula connectivity is important for cue-induced craving in nicotine-dependent smokers. Addict Biol 20:407-14
McClure, Erin A; Gipson, Cassandra D; Malcolm, Robert J et al. (2014) Potential role of N-acetylcysteine in the management of substance use disorders. CNS Drugs 28:95-106
Bentzley, Brandon S; Jhou, Thomas C; Aston-Jones, Gary (2014) Economic demand predicts addiction-like behavior and therapeutic efficacy of oxytocin in the rat. Proc Natl Acad Sci U S A 111:11822-7
Reichel, Carmela M; Gilstrap, Meghin G; Ramsey, Lauren A et al. (2014) Modafinil restores methamphetamine induced object-in-place memory deficits in rats independent of glutamate N-methyl-D-aspartate receptor expression. Drug Alcohol Depend 134:115-22
Cason, Angie M; Aston-Jones, Gary (2014) Role of orexin/hypocretin in conditioned sucrose-seeking in female rats. Neuropharmacology 86:97-102
Moran-Santa Maria, Megan M; Flanagan, Julianne; Brady, Kathleen (2014) Ovarian hormones and drug abuse. Curr Psychiatry Rep 16:511
McClure, Erin A; Acquavita, Shauna P; Dunn, Kelly E et al. (2014) Characterizing smoking, cessation services, and quit interest across outpatient substance abuse treatment modalities. J Subst Abuse Treat 46:194-201
Koch, F R; Wagner, C L; Jenkins, D D et al. (2014) Sex differences in cerebral blood flow following chorioamnionitis in healthy term infants. J Perinatol 34:197-202
Guille, C; Clark, S; Amstadter, A B et al. (2014) Trajectories of depressive symptoms in response to prolonged stress in medical interns. Acta Psychiatr Scand 129:109-15
Parsegian, Aram; See, Ronald E (2014) Dysregulation of dopamine and glutamate release in the prefrontal cortex and nucleus accumbens following methamphetamine self-administration and during reinstatement in rats. Neuropsychopharmacology 39:811-22

Showing the most recent 10 out of 62 publications