NIH Research Festival
Genetic variation in the dopamine transporter (DAT1/SLC6A3) has been associated with alcohol dependence. The 10A repeat allele of the variable number of tandem repeats (VNTR) polymorphism has been associated with greater DAT1 expression, and greater increases in alcohol-induced stimulation and mood. The objective of this study was to characterize the effect of DAT1 variation and the role of sex differences on intravenous alcohol self-administration (IV-ASA) in non-dependent drinkers. Healthy non-dependent drinkers (N=70) ages 21-45 completed a progressive-ratio IV-ASA session using the Computer-Assisted Infusion System (CAIS). The session consisted of an initial 25-min priming phase, where participants were prompted to push a button to receive individually standardized alcohol infusions, followed by a 125-min phase during which they were required to push the button an increasing number of times, using a progressive-ratio schedule, for additional alcohol infusions. Results showed strong DAT1 by sex interaction effects on IV-ASA measures. Male 10A homozygotes pressed for greater number of rewards and higher peak BrAC compared to 10A females, while 9A males pressed for less alcohol than 9A females. Subjective response as measured by the DEQ also showed a similar pattern, with 10A males reporting greater subjective responses for “intoxication” and “wanting alcohol” following the priming interval compared to 10A females, while 9A females reporting higher subjective responses compared to 9A males. Additionally, 10A homozygotes showed higher sensitivity to reward on the SPSRQ, and a trend for higher sensation-seeking on the UPPSP scale compared to 9A carriers.
Scientific Focus Area: Social and Behavioral Sciences
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