The general goal of the proposed research is to further our understanding of the interaction of limbic regions of the brain in fear, stress, and anxiety and in mediating the anxiolytic properties of anti-anxiety drugs. There is a body of evidence that suggests that fear or anxiety is the product of the mutually inhibitory interaction of anxiogenic structures such as the amygdala and anxiolytic structures such as the lateral septum. An understanding of the action of anxiospecific drugs must take into account the interaction of these brain regions. Two general sets of experiments are proposed. The first group of experiments will examine the role of the septum, amygdala and related structures in mediating that action of benzodiazepines and other anxiospecific agents. These experiments will use systemic and intracranial administration of drugs in combination with lesions to evaluate the role of these structures in mediating the action of benzodiazepines and related drugs. These manipulations will be evaluated behaviorally using two standard tests of anxiolytic action, the water-lick conflict paradigm and the elevated plus-maze. The second group of experiments will be devoted to the recording of single-unit activity in the limbic structures. Single unit activity will be examined in both the awake, freely-moving preparation and in the acute anesthetized preparation. In the awake preparation the effects of anxiospecific drugs will be tested on spontaneous unit activity and on unit activity conditioned to the experimental context and to specific conditioned stimuli. The goal of this research is to directly relate activity in brain regions associated with anxiety to the behavioral effects of anxiospecific drugs. The acute preparation will combine stimulation and recording to determine the nature of the mutual influence of septum and amygdala.
