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2018 Abstracts

Sex Differences in Ethanol Modulation of Dopamine Release in the Mesolimbic Reward System

Mandy Parsons, Brigham Young University

As the most abused legal drug in the world, the prevalence of alcohol addiction indicates a need for change and the discovery of the processes that will enable researchers to break the cycle of addiction. Current dogma holds that dopamine (DA) release in the nucleus accumbens (NAc) within the mesolimbic pathway is rewarding. Studying the effects of drugs on DA release sheds light on the mechanism of release and the possible discovery of treatment that might aid in the prevention and treatment of addiction. The relative dearth of animal studies conducted in females has led NIH to require researchers to consider sex as a variable in their studies in order to elucidate key sex related differences. However, despite these mandates, research has not been conducted on the effects of ethanol throughout the menstrual cycle. In human females, Ryback has determined that chronic alcohol consumption does disrupt the menstruation cycle in humans. (Ryback, 1977). This project’s purpose is to determine how the effects of alcohol on DA release in the NAc differ throughout the menstrual cycle thus improving our understanding of the neural substrates of alcohol addiction in women. Preliminary data has shown that while males show enhanced DA release by ethanol, females are characterized by a biphasic response consisting of enhancement followed by inhibition. Microdialysis trials are being employed in which a guide cannula is implanted in the NAc. A probe is inserted into the guide cannula and samples are taken by flowing artificial cerebral spinal fluid (aCSF) through the probe in order to collect dialysate samples every twenty minutes. After a baseline is established, ethanol is injected and samples are taken for the next three hours. Analysis is done using an HPLC to preform electrochemical separations. Using a variety of alcohol doses will create a dose response curve for alcohol in each phase of the menstruation cycle. The comparison of dose response curves throughout each phase will determine changes in alcohol mediated DA release. It is expected that preliminary conclusions can be reached regarding how DA release in response to alcohol is affected throughout proestrus, estrus, and diestrus in the female menstruation cycle. It is hoped that these conclusions will lead to better treatments for both men and women in conditions such as alcohol use disorder. Ryback, R. S. (1977). Chronic alcohol consumption and menstruation. JAMA, 238(20), 2143-2143.