This project concerns the subjective and physiological responses to drug challenges among individuals at different levels of risk for substance abuse. The high risk participants have either a documented first degree family history of alcoholism, or possess dopamine D2 receptor gene polymorphisms that may confer genetic risk for substance abuse. The low risk participants are sampled from similar populations, but do not possess these characteristics. These high risk individuals are old enough (21 to 25 years) to have had some alcohol experience, but are screened to rule out current or past alcohol abuse or dependence. Participants are exposed to drug challenges that include oral alcohol in a moderate dose, and on separate occasion, a low dose of oral methylphenidate. The alcohol challenges are presented at the same dose on different days in order to assess the development of chronic tolerance and/or sensitization, and to determine the reliability and stability of the subjective and cardiovascular responses to alcohol. The methylphenidate challenges are presented to some participants at several different dosages (including placebo) on different days in order to assess the dose dependency of these pharmacological effects. Results indicate that participants with family histories of alcoholism demonstrate greater """"""""reward"""""""" from alcohol, reflected in larger subjective responses to alcohol in positive mood, more general motor activation, and greater stress response dampening in hormonal responses to the drug. Preliminary results with methylphenidate indicate measurable responses to the drug, but a slightly higher dose has been added to the protocol to achieve more robust subjective and cardiovascular effects so that differences as a function of risk for substance abuse may be detected more effectively.
