Anxiety disorders are the most prevalent psychiatric disorders and appear to be a heterogenous group of disorders. The neurobiology of anxiety disorders is still poorly understood. However, several limbic structures have been consistently implicated in the neurobiological mechanisms underlying anxiety such as the hypothalamus, amygdala, and others. Several brainstem structures such as the locus ceruleus and the raphae nuclei have also been implicated in the etiology of anxiety disorders. The posterior hypothalamus appears to be a key region in the expression of anxiety with a neuronal circuit capable of eliciting the physiological and behavioral components of anxiety, especially resembling a panic attack. Many CNS regions implicated in anxiety, such as the amygdala and locus ceruleus appear to interact with the hypothalamus and elucidation of these interactions will significantly expand our understanding of anxiety disorders. This study will examine these mechanisms by local microinjection of drugs and pharmacologically manipulating neurotransmitter systems in rats and studying the effects of these procedures on heart rate, respiration, blood pressure, catecholamine levels and locomotion as well as three laboratory tests of anxiety that appear to regulate anxiety at each of the above mentioned CNS sites. Specifically, this research proposes to: 1) characterize the effects of modifying GABA neurotransmission in the posterior hypothalamus of rats on anxiety with particular emphasis on the possible involvement of this region in the etiology of panic disorders; 2) study the role of amygdala in anxiety local pharmacological manipulations of locus ceruleus on anxiety and determine the interaction of posterior hypothalamus with this region; 3) study the effects of pharmacological manipulations of locus ceruleus on anxiety and determine the interaction of the posterior hypothalamus with the locus ceruleus. The results of the proposed study will increase our understanding of the anxiety disorders and might help us devise better pharmacological strategies for their treatment.
