The long-term objective of this R01 is to identify, using electrophysiological techniques, CNS mechanisms mediating high alcohol seeking behavior. The specific aims are designed to test the hypothesis that innate differences in the mesolimbic dopamine (DA) system underlie genetic vulnerability to high alcohol seeking behavior. Rat lines selectively bred for disparate alcohol drinking will be used: the alcohol-preferring P, alcohol-non-preferring NP, high alcohol drinking HAD and low alcohol drinking LAD lines. The individual experiments will focus on the neuronal activity of ventral tegmental area (VTA) DA neurons. Extracellular recording techniques and iontophoresis will be used to determine differences in basal activity among P, NP, HAD and LAD rats, differences in receptor sensitivities to NMDA in P and NP rats and differences in neuronal activity in P and HAD rats during chronic alcohol consumption and abstinence. The results of this project will provide fundamental insights regarding electrophysiological parameters involved in high alcohol seeking behavior. Such information will be germane for developing pharmacotherapies for the treatment of alcoholism and alcohol abuse.