Individual Differences in Alcohol Effects Among High- and Low- Impulsive Sensation Seekers Kelly, T.H., Robbins, G., Martin, C.A., Marczinski, C.A. and Fillmore, M.T. Departments of Behavioral Science, Psychiatry and Psychology, University of Kentucky Abstract Previous studies indicate that high sensation seekers are at increased vulnerability to drug abuse in part as a result of enhanced sensitivity to the reinforcing and other behavioral effects of drugs. This ongoing study examines the effects of alcohol in groups of high and low impulsive sensation-seeking adults matched on levels of alcohol and drug use. Fifteen of twenty healthy volunteers scoring in the top and bottom quartiles of gender-adjusted population norms on the impulsive-sensation seeking scale of the Zuckerman-Kuhlman Personality Questionnaire (6 high- and 9 low- impulsive sensation seekers) completed 7 test days in which assessments were completed before (i.e., baseline) and after oral dose administration at times chosen to equate blood alcohol levels on the ascending and descending portions of the blood- alcohol curve. Placebo was administered on the first test day, during which data are collected but not analyzed. Each of three doses (0, 0.45 and 0.65 g/kg) was then tested under double-blind conditions on 2 days according to a randomized-block design. Alcohol impaired performance on psychomotor, impulsivity and attention tasks, increased heart rate, and engendered both stimulant- and sedative-like verbal reports of drug effect. Importantly, the magnitude of alcohol effects varied as a function of ascending and descending blood alcohol levels. High sensation seekers reported significantly greater reports of sedation on the Alcohol Sedation-Stimulation Scale and Light-Headed on the Visual-Analog Scale during both ascending and descending blood alcohol levels, suggesting that high sensation seekers are more sensitive to the acute behavioral effects of alcohol than low sensation seekers. Supported by DA and RR Method Subjects: Fifteen healthy adults, ages 21 to 30, completed medical screening and gave written consent prior to participating in outpatient studies lasting 4.5 hours per day (or until BAL was <= 0.02 g/dl) for seven days. Six were classified as High Sensation Seekers, and nine were classified as Low Sensation Seekers. All subjects received task training and practice prior to the study until stable performance was observed. Sensation-Seeking Status: All subjects completed items from the impulsive sensation- seeking scale of the Zuckerman-Kuhlman Personality Questionnaire. Those who scored in the upper and lower 25% of the population, based on established norms, were classified as High and Low Sensation Seekers, respectively. Drug: Each dose of alcohol (0, 0.45, 0.65 g/kg) was administered on two separate days according to a randomized block design. An additional placebo dose was administered on the first study days during which data were collected but not analyzed. Doses were administered under double-blind conditions. Procedure (Table 1): Daily schedules were constant throughout the study. Subjects completed 30-minute sessions before drug administration, 30 minutes following drug administration, and 75 and 90 minutes following drug administration of the and doses, respectively. Each session consisted of verbal report of drug effects (ARCI, VAS, ASSS), psychomotor (digit-symbol substitution), impulsivity (Cued RT), and attention (rapid information processing) measures. Data Analysis: A mixed-model ANOVA was conducted with one between- (High vs. Low Sensation Seeking Status) and two within-group (dose x 3 and time x 3) factors. Results Blood Alcohol Levels (BAL’s, Table 2) Dose-related increases in BAL’s were observed during both ascending and descending level sessions for low and high sensation seekers. No significant differences in BAL’s were observed between low and high sensation-seeking groups, although means during ascending level were significantly higher than during descending level for the 0.45 g/kg dose. Significant Alcohol and Alcohol x Time Interactions (Table 3) ARCI: Alcohol increased ratings on the PCAG, LSD and A scales, although effects on the A scale occurred only during ascending BAL’s. VAS: Alcohol increased ratings on the Stimulated, Sedated, Light-Headed, Sick-to-Stomach, High, Feel Drug and Like Drug scales. ASSS: Alcohol increased ratings on the Stimulated and Sedated composite scales, with magnitude of effect varying as a function of ascending and descending levels. DSST: Alcohol decreased total trial rate and performance accuracy. RIP: Alcohol increased reaction time (i.e., decreased trial rate) and decreased accuracy, although effects on accuracy were limited to ascending levels. Cued RT : Alcohol increased reaction time (i.e., decreased trial rate) and decreased accuracy. Cardiovascular: Alcohol increased heart rate, although effects were limited to descending levels. Significant Sensation-Seeking Status x Alcohol x Time Interactions Figure 1 presents the effects of alcohol on VAS ratings of Light-Headed separately for low and high sensation seekers. Significant alcohol x time interactions were observed for both low and high sensation seekers, although the magnitude of drug effect was clearly greater for high sensation seekers. Significant sensation seeking status x time interactions were observed at the 0.45 and 0.65 g/kg dose conditions. Significant sensation-seeking x alcohol dose interactions occurred during both ascending and descending level sessions, although the magnitude of the interaction was clearly greater during ascending level sessions. Figure 2 presents the effects of alcohol on the ASSS composite Sedated scale separately for low and high sensation seekers. Significant alcohol x time interactions were observed for both low and high sensation seekers, although the magnitude of drug effect was clearly greater for high sensation seekers. Significant sensation seeking status x time interactions were observed at all dose conditions. Significant sensation-seeking x alcohol dose interactions occurred during both ascending and descending level sessions. Significant sensation-seeking status x dose x time interactions were also obtained on VAS ratings of Stressed and Anxious (data not shown). For VAS Stressed, significant alcohol x time interactions were observed for both low and high sensation seekers; significant sensation seeking status x time interactions were observed at the 0.45 and 0.65 g/kg dose conditions, and significant sensation-seeking x alcohol dose interactions occurred during both baseline and descending level sessions, with alcohol effects being greater among low sensation seekers. For VAS Anxious, significant alcohol x time interactions were observed for both low and high sensation seekers; significant sensation seeking status x time interactions were observed at at the 0.45 and 0.65 g/kg dose conditions, and significant sensation-seeking x alcohol dose interactions occurred during baseline, ascending and descending level sessions, with alcohol effects being greater among low sensation seekers. No group differences in drug use or other psychiatric symptoms, including conduct disorder, ADHD, depression or scores on the BSI, were observed. Conclusions 1. The effects of alcohol on subject report measures of drug effect were consistent with the results of previous studies. Typical stimulant- and sedative-like effects were observed on ARCI, VAS and ASSS scales. Dose-related increases were observed on several scales that have been associated with the reinforcing effects of drugs (i.e., VAS Like Drug; ARCI PCAG and A scales; ASSS Stimulated and Sedated scales). 2. High sensation-seekers exhibited greater sensitivity to the effects of alcohol on VAS ratings of Light-Headed and the ASSS composite Sedated scale. Group differences in drug effects were observed on other scales, as well, but effects did not reach statistical significance. To the extent that these measures are associated with the reinforcing effects of alcohol, the data suggest that the reinforcing effects of alcohol may be greater in high sensation seekers than in low sensation seekers. 3. The effects of alcohol on measures of task performance were also consistent with the results of previous studies. Typical sedative- like effects were observed on DSST, RIP and Cued RT task performance. Differences in impairment as a function of ascending and descending alcohol levels varied across tasks. 4. The effects of alcohol on several subject report, cardiovascular and task performance measures varied as a function of ascending and descending alcohol levels, suggesting that the functional effects of alcohol vary as a function of relative changes in BAL. 5. High sensation seekers are more likely than low sensation seekers to engage in a variety of high-risk behaviors, including drug use. These data suggest that while high sensation-seekers may be more likely to initiate experimentation with drug use, they may also be more vulnerable to the reinforcing effects of alcohol, and thereby be at greater risk for developing repeated patterns of drug- seeking behavior. Table 1 Daily Schedule Time (Min)Event 00Intake Assessment Baseline Session Dose Administration 30Ascending Session 75/90Descending Session Discharge Assessment Session Tasks Addiction Research Center Inventory (ARCI): The 49-item short form of the true- false ARCI provided reports of drug effects on five scales: LSD, Amphetamine (A), Benzedrine (BG), Morphine-Benzedrine (MBG) and Pentobarbital, Chlorpromazine, Alcohol Group (PCAG). Visual-Analog Rating Scales (VAS): Ratings of Stimulated, Sedated, Light-Headed, Drug Effect and Like Effect were obtained by placing marks on a 100-unit line anchored with "Not at all" on the left and "Extremely" on the right. Alcohol Sedation-Stimulation Scale (ASSS): Composite scores for Sedation and Stimulation were obtained by summation of ratings from 14 adjectives on a scale from 0 to 10 with 0 being “Not at all” and 10 being “Extremely” Digit-Symbol Substitution Task (2 minutes): Nine random 3-row by 3-column arrays of asterisks and dashes (one asterisk per row), labeled 1-9 from left to right, were displayed at the top of the computer monitor. A randomly generated number, between 1 and 9, was displayed in the center of the monitor, indicating which of the nine arrays should be reproduced on a given trial. Subjects reproduced an array by pressing the buttons on a 3-row by 3-column keypad that corresponded to the positions of the asterisks in the screen array. Rapid Information Processing Task (RIP, 5 minutes): Single digits were presented in the center of the monitor, and subjects were instructed to press a key whenever three consecutive even or odd digits were presented. Following correct responses, the speed of digit presentation was increased, and following incorrect responses or missed signals, the speed of digit presentation was decreased. Cued Reaction Time (Cued RT, 15 minutes): Subjects are required to respond as quickly as possible when green rectangles are presented on the screen, and to make no response when blue rectangles are presented. Horizontal and vertical white rectangles predicting the subsequent color presentation on 60% of trials were presented prior to the color cue. Cardiovascular: Heart rate and blood pressure were recorded immediately after completing computer tasks. ASSS Sedation VAS Light-Headed Figure 1: Effects of alcohol on visual-analog scale ratings of Light-Headed as a function of time (Baseline, Ascending, Descending) following dose administration for low (left panel) and high (right panel) sensation seekers. Error bars represent + 1 SEM. Figure 2: Effects of alcohol on the ASSS composite Sedated scale as a function of time (Baseline, Ascending, Descending) following dose administration for low (left panel) and high (right panel) sensation seekers. Error bars represent + 1 SEM. Rating Score