Hippocampal inhibition of pituitary-adrenocortical function in female rats

Selective Hippocampal Lesions Do Not Increase Adrenocortical Activity

“…These results contrast with reports of adrenocortical hyperactivity after large nonselective mechanical or electrolytic lesions of the hippocampus (Fendler et al, 1961;Kim and Kim, 1961;Knigge, 1961;Moberg et al, 1971;Murphy et al, 1979;Fischette et al, 1980;Wilson et al, 1980;Sapolsky et al, 1984Sapolsky et al, , 1991Herman et al, 1989). Discrepant effects on corticosterone secretion after hippocampal lesions have previously been attributed to differences in recovery time between surgery and experimentation (Jacobson and Sapolsky, 1991).…”

“…Physiological evidence from various sources indicates that hippocampal activity exerts an inhibitory influence on the HPA axis (Jacobson and , but does normal HPA activity depend on this hippocampal input or can other control systems provide similar inhibition? Several studies have shown that damage to the hippocampus increases basal glucocorticoid secretion (Fendler et al, 1961;Kim and Kim, 1961;Knigge, 1961;Moberg et al, 1971;Fischette et al, 1980;Wilson et al, 1980;Sapolsky et al, 1984Sapolsky et al, , 1991Herman et al, 1989), but these lesions were made either by aspiration or by transection of the fimbria-fornix and caused damage to bypassing fibers as well as adjacent brain systems, including the parahippocampal cortices and several subcortical structures. Other studies failed to identify a hippocampal inhibitory influence on the HPA axis (Coover et al, 1971;Lanier et al, 1975;Conforti and Feldman, 1976;Smotherman et al, 1981;Bradbury et al, 1993;Herman et al, 1995) but there was only incomplete damage to the hippocampus in these studies.…”

Glucocorticoid-sensitive hippocampal neurons are involved in terminating the adrenocortical stress response.

“…Within this complex framework, the hippocampus has been shown to have an inhibitory influence on HPA activation under a variety of circumstances. For example, destruction of the hippocampus or its efferents leads to increases in corticotropin and corticosterone under basal conditions (4-7) and during stress (5,6,8,9). Furthermore, stimulation of most parts of the hippocampus limits the extent of HPA activation to an array of stressors (10)(11)(12)(13).…”

“…For example, hippocampectomized subjects are less sensitive to the suppressive effects of exogenous glucocorticoids on HPA secretion (6). Moreover, corticotropin (ACTH) is increased after hippocampectomy and the difference in corticotropin levels between lesioned and sham-lesioned animals is abolished by adrenalectomy, suggesting that the relative increase in corticotropin due to the lesion resulted from lesion-induced disinhibition from corticoid-feedback suppression (5). This evidence that circulating glucocorticoids exert some of their feedback effects via the hippocampus suggests that such actions are mediated by the hippocampal glucocorticoid receptor.…”

“…However, the hippocampus has been persistently implicated as an inhibitory influence on the hypothalamic-pituitary-adrenocortical (HPA) axis. Destruction of the hippocampus, for example, leads to hypersecretion of glucocorticoids under basal and stressed conditions (4)(5)(6)(7)(8)(9). Furthermore, stimulation of most parts of the structure inhibits stress-induced HPA activation (10)(11)(12)(13).…”