This project is an opportunity to identify biological mechanisms underlying binge drinking and their relationship to individual differences in the capacity to reduce drinking. We propose to characterize serotonin transporter (SERT) function using an immortalized human lymphoblastoid cell line (LCL) model among Binge and Non-Binge drinking adults recruited from R01-AA014988. This ongoing study has 4 phases: (1) participants complete impulsivity measures during a simulated alcohol binge procedure and/or L-tryptophan depletion;(2) drinking patterns between groups are characterized using continuous transdermal alcohol monitoring for 4 weeks;(3) Binge drinkers complete a 12-week contingency management procedure designed to identify individual differences in the capacity to reduce alcohol consumption, where contingencies are determined using results obtained from the transdermal alcohol monitoring device;and (4) patterns of drinking are re-evaluated for 3 months to assess residual effects on drinking patterns. The parent project is testing how behavioral and biological processes contribute to binge drinking, and elucidating how these relate to an individual's ability to reduce alcohol use in the """"""""real world"""""""". Reductions in 5-HT in the synaptic cleft are thought to be associated with problematic patterns of drinking;some have hypothesized that 5-HT reductions are due to increased presynaptic SERT function that removes 5-HT from the cleft. However, inconsistent results from studies of SERT expression and function in the brain and platelets may be due to """"""""state dependent"""""""" (e.g., age, alcohol intake, medications) influences on SERT. LCLs allow for examination of the SERT system under controlled conditions (i.e., without """"""""state"""""""" influences). We will use the LCL model to characterize SERT: (A) Expression - the total number of transporters;(B) Distribution - the proportion of SERT on the cell surface versus total cellular SERT;and (C) Function - the active transport of 5-HT into the cell. This proposal will investigate how innate differences in LCL SERT function relate to the outcomes observed in the parent project. Because SERT expression and distribution are mechanisms underlying SERT function, we will measure all three to provide a more complete understanding of observed individual differences. The proposed aims are: (1) comparing LCL SERT characteristics between Binge and Non-Binge drinkers;(2) determining the relationship between LCL SERT function and changes in impulsivity observed after a simulated alcohol binge (and acute L-tryptophan depletion);(3) determining how an individual's capacity to reduce drinking (during 3- month contingency management and 3-months follow-up) relates to LCL SERT function;and (4) measuring SERT characteristics in both LCLs and platelets prior to and after intervention, where drinking is eithe unaffected or significantly reduced. Our study will advance our understanding of how SERT function relates to an individual's capacity to reduce drinking and help identify potential biological mechanisms.
Alcohol binge drinking produces dangerous levels of intoxication and acute health consequence that confer immediate risks to both the individual and society. The proposed study will provide fundamental information on how underlying biological and behavioral processes relate to individual differences in the ability to reduce alcohol consumption. The results of this study will inform the development of treatments aimed at this unique population of problem drinkers, and inform us about how differences in these markers might be used by clinicians to match treatment plans to specific individuals.
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