Adaptation of Subjective Responses to Alcohol is Affected by an Interaction of GABRA2 Genotype and Recent Drinking.

Session designSubjective perceptions of alcohol were collected at the beginning and end of Block 0, Block 1, and Block 2, then averaged to give a single measurement for each block.

The Subjective Perceptions AssessmentThe 7 questions were presented one at a time, in random order, at the beginning and end of each block. For questions 1–6, subjects rated their perceptions by moving a pointer along a visual analog scale anchored at 5 positions (coded from 0–100). For question 7, subjects estimated how many drinks it would take to create their current perceptions by moving a pointer on a scale ranging from 0 to 10 in half-drink increments. After the first assessment, the pointer was presented in the position selected for that question on the previous assessment. During the practice session, subjects were instructed to place the slider at 0 for number of Drinks, and at “Not at all” for Intoxicated and Enjoy. For Stimulated, Tired, Relaxed and Anxious, they were told to move the slider to reflect their current perceptions, independent of the effect of alcohol. Subjects were required to read each question aloud before moving the slider. Responses were automatically time-stamped and logged; subjects were able to answer all 7 questions in less than a minute.

Recent drinking history by subgroupMean and SEM for recent drinking history (drinks/drinking day in the last 30 days) grouped by gender, family history of alcoholism, GABRG1 genotype, and GABRA2 genotype. * indicates P=0.001.

Initial and Adaptive Response to AlcoholMean and SEM of (A.) initial and (B.) adaptive response to alcohol scores for each of the seven subjective measures are shown. Black bars represent the mean scores for all subjects during the alcohol infusion; striped bars represent the mean scores during the placebo (saline) infusion; estimated number of drinks was multiplied by 10 so that it could be shown on the same scale as the other measures. Negative values of the adaptive response to alcohol reflect acute (within-session) tolerance (return toward baseline), while positive values reflect acute sensitization.

Adaptive response to alcohol as moderated by genotype and recent drinking historyThis graph illustrates the significant genotype by recent drinking history interaction. Mean and SEM for PC1 is shown for GABRA2 rs279858 genotypes, with subjects divided by a median split into either lower (black bars) or higher (striped bars) drinks per drinking day. Group N’s are indicated above the bars. All groups, on average, showed tolerance, but the relative degree varied.