Career Development Award: Center for Appalachian Research in Environmental Sciences: E-Cigarette Aerosol and Hormone Interactions on Neurobiology and Cyclicity

Abstract SPECIFIC AIMS Smoking remains a leading preventable cause of death in the United States, with high relapse rates. Although combustible cigarette use has declined in recent years, there has been a surge in electronic nicotine delivery systems (ENDS) use, which is increasingly being linked to health issues such as cancer. The availability of chemical flavorants in ENDS products contributes to their use as they are otherwise banned in combustible products, and these flavorants have been shown to increase reward-related behavior as well as brain reward circuitry. Women have more difficulty maintaining smoking cessation than men including experiencing greater withdrawal symptomatology and higher prevalence of relapse, as well as lower response to currently available pharmacotherapeutics such as the patch. Craving and relapse to smoking vary in women as a function of their menstrual cycle phase. Specifically, increases in the naturally cycling estrogen, 17ß-estradiol (E2) is associated with addiction vulnerability. Thus, ovarian- derived and contraceptive hormones interact with nicotine in a clinically significant way. Here, we propose a systematic empirical examination of how ovarian and contraceptive hormones interact with vaporized chemicals contained in ENDS products, which will set the stage for an extramural grant proposal to further evaluate these relationships. In aim 1, we will determine how passive exposure to different chemicals contained in e-cigarette aerosol impact glutamate plasticity in the nucleus accumbens core (NAcore), a key brain reward region heavily implicated in addiction processes, as well as cyclicity measured via vaginal cytology. In aim 2, we will determine how contraceptive hormones (specifically, ethinyl estradiol and levonorgestrel) interact with either self- administered or yoked (second hand) exposure to e-cigarette aerosol to alter NAcore glutamate plasticity and amount of vapor consumed. Together, these studies will lay a foundation for a larger R01 to evaluate other environmental pollutants contained in ENDS products on behavior and biology.