Numerous studies show that a low level of response to the intoxicating effects of alcohol is considered a risk factor for future alcoholism. However, assessing this sensitivity usually requires administering a controlled dose of alcohol, which has a number of inherent problems. Early observations in our lab suggest that the response to anesthetics that show cross tolerance with alcohol, like ketamine, are blunted in nonhuman primates at risk for high alcohol intake, and may be a viable measure of future alcohol consumption. This study was designed to test potential predictors of future alcohol consumption using the change in ketamine across repeated exposures (i.e., tolerance). In addition, potential mediating factors of alcohol consumption, including early temperament and behavior, were assessed. Subjects were 16 three-year-old, alcohol naïve rhesus macaque males raised by their biological mothers. Ketamine Exposure-Each subject was exposed to three 10.0 mg/kg intramuscular doses of ketamine. The time from injection to recovery from anesthetic was recorded for each dose, to be used as a measure of subject's sensitivity and developed tolerance. Alcohol Intake Assessment-Two weeks after the final ketamine dose, subjects were allowed ad libitum access to a palatable 8.4% alcohol solution for two-hours a day, five days a week, for six weeks. During the Two-Choice phase of testing, subjects were simultaneously given ad libitum access to the 8.4% alcohol solution and to a sweetened solution for two-hours a day, five days a week, for four weeks. Solution consumption was recorded daily and averaged across the weeks for each phase of alcohol testing. Temperament and Behavior-As infants, all subjects participated in a bio-behavioral assessment (BBA), when they were between 90 and 120 days of age. Data collected during the BBA on subjects' temperament (Vigilance, Gentleness, Confidence, and Nervousness) and Behavior (Activity and Emotionality) were used in analyses. Results showed a relationship between the tolerance developed between ketamine doses and average alcohol consumption during the Alcohol-Only phase (r = 0.61, R2 = 0.372, F (1,14) = 8.300, p = 0.012). Average alcohol consumption during the Alcohol-Only phase was also related to ratings of Confidence (r = 0.499, R2=0.249, F(1,14)=4.647, p = 0.049), Activity (Day 1: r = 0.503, R2 = 0.253, F(1,14) = 4.732, p = 0.047; Day 2: r = 0.455, R2 = 0.207, F(1,14) = 3.652, p = 0.077), and Emotionality (r = 0.466, R2 = 0.217, F(1,14) = 3.885, p=0.069). The results of this study suggest that change in ketamine recovery time and early life temperament and behaviors may be measures of future risk for alcohol abuse disorders. This data is limited by the small sample size and future study is necessary to further tease out the relationships between these variables and alcohol consumption.
| Identifer | oai:union.ndltd.org:BGMYU2/oai:scholarsarchive.byu.edu:etd-5185 |
| Date | 27 June 2014 |
| Creators | Sorenson, Andrea Nichole |
| Publisher | BYU ScholarsArchive |
| Source Sets | Brigham Young University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Theses and Dissertations |
| Rights | http://lib.byu.edu/about/copyright/ |
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