We are investigating the neurobiology of anxiety from three approaches. We have used the anatomic method of quantitative in vitro autoradiography to map the regional distribution of the corticotropin releasing factor (CRF) receptor and the benzodiazepine receptor in brain. Using local microinjections into receptor dense areas, we have begun to test specific brain regions for behavioral effects relevant to anxiety. In a second approach, we have studied developmental antecedents of anxiety. Ultrasonic isolation calls in rodent pups are increased in anxious strains and appear selectively responsive to benzodiazepines. Finally, we have looked for differences in brain receptors in "anxious" animals. Maudsley reactive rats have an increased number of adenosine receptors, but no difference in the number of benzodiazepine receptors compared to the Maudsley non-reactive strain. Studies in "anxious" rhesus monkeys reveal that the benzodiazepine receptor inverse agonist Beta-carboline-3-carboxylic acid-ethyl ester (Beta-CCE) has different behavioral effects depending on social context.