LESIONS OF THE HIPPOCAMPAL EFFERENT PATHWAY (FIMBRIA-FORNIX) DO NOT ALTER SENSITIVITY OF ADRENOCORTICOTROPIN TO FEEDBACK INHIBITION BY CORTICOSTERONE IN RATS

The hypothalamic-pituitary-adrenal (HPA) axis controls the diurnal and stress-induced release of adrenal corticosteroids into the general bl ood circulation. In turn, corticosteroids inhibit the HPA axis under b asal conditions and during stress through occupation of their receptor s (types I and II) in the brain by closing a negative feedback loop. T he primary site in the brain at which corticosteroids act to inhibit t he HPA axis has not been identified. High concentrations of both types of receptors are found in neurons of the hippocampal formation, a str ucture which has been reported by some, but not others, to control act ivity within the HPA axis by serving as a major negative feedback site . In many of these past studies, blood was collected after extensive h andling or exposure to ether, conditions which do not favor the detect ion of basal hormone concentrations. To address these controversies, w e tested the feedback sensitivity of the anterior pituitary hormone re sponsible for corticosteroid production, adrenocorticotropin (ACTH), t o corticosterone (B), the main corticosteroid in rats, in total fornix - and, as controls, cortex-lesioned rats. All rats were given vascular catheters to avoid any handling-induced differences in plasma B or AC TH when sampling blood. In some experiments, fornix- and cortex-lesion ed rats were adrenalectomized and given 1 of 3 doses of exogenous B pr ovided in a subcutaneous pellet to ensure that plasma B was equal in d ifferent lesion groups. We hypothesized that if the hippocampal format ion were an important site of B-mediated inhibition of the HPA axis, f ornix-lesioned rats would have higher plasma B as a result of increase d endogenous secretion in the morning or the evening compared to corte x-lesioned rats in rats with adrenal glands. In addition,we hypothesiz ed that adrenalectomized fornix-lesioned rats given the same low to mo derate levels of exogenous constant B would have higher basal and stre ss-induced ACTH than cortex-lesioned rats. Diurnal plasma B was not af fected by fornix lesions in intact rats. Moreover, basal ACTH measured in the morning and the evening and stress-induced ACTH was the same i n adrenalectomized fornix- and cortex-lesioned rats with constant exog enous B. We conclude, therefore, that information about occupancy of B receptors in the hippocampus carried by the fornix primarily subserve s functions which do not directly regulate activity in the HPA axis.