Project Summary Deficits in response inhibition are observed in alcohol dependence and are proposed as an endophenotype of the disorder. It is unclear whether deficits in response inhibition increase vulnerability to alcohol dependence of whether impaired response inhibition is a consequence of alcohol use. Importantly, these questions can most conclusively be investigated using a longitudinal approach. However, studies investigating the neural mechanisms of response inhibition have primarily focused on adult models. Experimentation with alcohol during adolescence is consistently reported to alter brain structure and function. This is because of the numerous on-going developmental processes during maturation, which makes adolescence a critical time in development marked by increased susceptibility to environmental insults. To date, there are few studies which attempt to understand how adolescent alcohol exposure alters cognition during both adolescence and adulthood. This is due in part to the short window of adolescence which poses a technical challenge because it precludes the use of well characterized decision-making behavioral paradigms. Our laboratory has recently developed a Cued Response Inhibition Task (CRIT) paradigm that assesses response inhibition, stimulus- response relationships, attentional processes and behavioral flexibility in adolescents or adults. Using this paradigm, we propose to measure single unit and local field potential activity in male and female adolescent and adult rats with adolescent alcohol or sucrose drinking histories. By performing simultaneous recordings in the orbitofrontal cortex (OFC) and dorsal striatum (DS), two regions heavily implicated in reward-seeking behaviors and hypothesized to mediate behavioral inhibition, these experiments will determine how adolescent alcohol exposure alters neural activity in adolescence (Aim 1), how adolescent alcohol exposure alters neural activity in adulthood (Aim 2) and how age influences neural circuitry necessary for response inhibition (Aims 1 and 2). We hypothesize that adolescent alcohol drinking will weaken coordination of neurons in the OFC, which in turn will reduce OFC-DM connectivity. Reduced functional connectivity between these regions will be associated with deficits in response inhibition, complementing work in human imaging where impaired frontal striatal connectivity during response inhibition is associated with increased severity of alcohol dependence.