Abstract # 50:

Scheduled for Thursday, June 19, 2008 05:00 PM-07:00 PM: Session 4 (Ball Rooms A and B) Poster Presentation

Individual Differences in Biobehavioral Profiles may Impact Drug Results

S. Howell1, M. Schwandt2, J. Champagne3, G. Westergaard3 and J. Higley4
1Mannheimer Foundation, Inc., Haman Ranch, P.O. Box 1235, Clewiston, FL 33440, USA, 2Section for the Study of Primate Models of Psychopathology, Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 3Alpha Genesis, Inc., 4Department of Psychology, Brigham Young University
     This study considers individual differences in the effect of Metyrapone on cortisol, behavior and ethanol consumption in rhesus macaques (Macaca mulatta). Cortisol is increased when a body’s stress response system is activated. Metyrapone blocks cortisol synthesis and may impact an individual’s stress response system and reduce anxiety-related alcohol consumption. Subjects included 5 adult males singly housed in enriched cages. A drug, recovery, washout, placebo-crossover design was used to consider the effects of metyrapone on ethanol consumption. An 8.4% sweetened ethanol solution was administered one hour daily and total volume consumed was measured at the end of the hour. Subjects were trained to cooperate with venipuncture for plasma cortisol testing and oral/placebo dosing. A focal animal sampling method was used to consider behavior (e.g., fear, aggression, exploration, and self-directed behavior) and t-tests were used for paired comparisons. Results suggest [t-tests, a=0.05] metyrapone led to a non-significant decrease in alcohol consumption over baseline levels for subjects with high baseline cortisol levels (37.9-41.8 ug/dl) and rates of exploratory behavior. In contrast, metyrapone led to a non-significant increase over baseline levels for subjects with lower baseline cortisol levels (22.0-30.0 ug/dl) and high rates of self-directed behaviors. These data need to be replicated with a larger subject sample. Differences in biology and behavior across individuals may impact drug effects. Research was conducted with support from NIAAA Contracts N01AA42002 and N01AA02018.