Clinical data and experimental pharmacology has led to the recognition of Panic Disorder as a clinical entity distinct related general anxiety conditions and to the identification of its role in the generation of agoraphobia. It has been hypothesized that differences in response to specific classes of drugs and heightened susceptibility resulting from early separation experiences help define the disorder. One crucial dataset involves the reproducible provocation of discrete panic episodes in susceptible patients through the administration of sodium lactate. In extensive preliminary work using unrestrained subjects, we have found that in response to lactate (versus dextrose controls), nonhuman primates show varying degrees of behavioral response which mirror human reports; moreover, pilot data suggest broad individual differences in threshold of response to different concentrations of lactate. As in humans, initial studies indicate that imipramine blocks the panic/distress pattern. We propose a program involving systematic behavioral observations and parallel cardiovascular and biochemical measures in blood and CSF, to determine genetic (species), sex and individual differences in response to a range of lactate dosages; the impact of early separation experience on later susceptibility; the role of learning in developing agoraphobia-like avoidance patterns; and, the capacity of specific classes of drugs, (tricyclic antidepressants, MAO inhibitors, and benzodiazepines) in blocking the emergence of panic and subsequent blocking of learned panic-associated patterns. These data will help characterize the behavioral and physiological parameters of the panic/distress syndrome, will provide prospective data on hypothesized etiologic and learning effects on its manifestations, and offer insights into the pharmacological treatment of the disorder and its sequelae.

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Suny Downstate Medical Center
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