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This project attempts to probe interrelationships between the central nervous system, immune and endocrine systems. The key departure was the discovery that certain synthetic copolymers stimulate hyperplasia of cortical lymphocytes in the thymus and increased motor behavior. These copolymers, polyphores, are monovalent cation-selective ionophores. During the past year, we developed evidence that T150R1 represents a new class of immunoendocrine modulators. It appears to induce corticosteroids by both a pituitary and an extra-pituitary mechanisms. It may bypass the pituitary either by acting directly on the adrenals, or by acting indirectly on immune cells, such as lymphocytes or macrophages, to induce ACTH or interferon, that can stimulate the adrenals. Its mechanism of action may be by altering cation flux in cells within the hypothalamic pituitary-adrenal axis, as well as cells of the immune system. Many studies attempting to relate behavioral and immunologic changes induced by the copolymers were conducted.

This project attempts to probe interrelationships between the central nervous, immune and endocrine systems. The key departure was the discovery that certain synthetic copolymers stimulate hyperplasia of cortical lymphocytes in the thymus and increased motor behavior. These copolymers, investigations suggested that these copolymers might mimic the activity of neuropeptides either by interacting with their receptors or by modifying cation fluxes across cell membranes. The experiments in this project have been designed to characterize the effects of polyphores more completely and to look for changes which might be attributed to the action of neurotransmitter analogues. Retrospective analysis of the first year's data demonstrated stimulatory effects of the polyphore copolymer on the thymus and on motor activity primarily in animals which had undergone severe stress. The current working hypothesis is that the ionophore copolymers somehow modify the reaction to stressful stimuli. This modification includes an increase in motor activity, a reduction in involution of the thymus and a stimulation of proliferation of cells in the cortex of thymus. During the coming year, animals will be treated with stessful conditions in a controlled fashion in an effort to test the hypothesis that the copolymer modifies the stress reaction. Several stressful stimuli, including food and water deprivation, immobilization and rewarding brain stimuli, will be evaluated.