Ž . Brain Research 858 2000 181–190 www.elsevier.comrlocaterbres Interactive report Influence of the ventral hippocampal formation on plasma vasopressin, hypothalamic-pituitary-adrenal axis, and behavioral responses to novel acoustic stress 1 Kendall W. Nettles a , Christine Pesold b , Morris B. Goldman a,b, ) a Department of Psychiatry, UniÕersity of Chicago, Chicago, IL 60637, USA b Psychiatric Institute, UniÕersity of Illinois in affiliation with UniÕersity of Chicago, Chicago, IL 60612, USA Accepted 2 November 1999 Abstract Ž . The ventral hippocampal formation vHF seems to constrain diverse responses to psychological stimuli, and disruption of this function may underlie severe neuropsychiatric diseases. In particular, the ventral subiculum inhibits hypothalamic-pituitary-adrenal axis Ž . HPA activity following psychological, but not systemic, stressors. Despite the difficulty in interpreting such HPA responses, they have been relied upon to further characterize vHF function, because increased HPA axis activity is implicated in neuropsychiatric disturbances, Ž . and reliance on behavioral and cognitive data is even more problematic. Plasma arginine vasopressin pAVP , which is inhibited by psychological stimuli and is also implicated in diverse neuropsychiatric diseases, provides a less ambiguous measure of CNS function. To test if its inhibition by psychological stress is also mediated by the vHF, we conducted two studies. In the first, pAVP and behavioral responses to novel acoustic stress were assessed in rats with bilateral excitotoxic lesions of the ventral subiculum and the ventral hippocampus. The subiculum lesions blocked the fall in pAVP and enhanced escape behaviors, whereas the hippocampal lesions produced responses intermediate to those in the subiculum-lesioned and control rats. In the second study, the pAVP response was similarly blocked by small lesions restricted to those vHF subfields which project to the neuroendocrine hypothalamus, compared to the response in animals with lesions in other vHF subfields. These results indicate that discrete projections from the vHF inhibit the pAVP response to psychological stimuli, and suggest that pAVP may provide a reliable probe of vHF activity. q 2000 Elsevier Science B.V. All rights reserved. Keywords: Hippocampal formation; HPA axis; Rats; Schizophrenia; SIADH; Vasopressin 1. Introduction The extensive projections from the hippocampal forma- tion to the hypothalamus in the brain are topographically organized, such that dorsal subfields innervate caudal hy- pothalamic nuclei, whereas ventral subfields innervate ros- w x tral nuclei 32,50 . Although the role of the dorsal hip- pocampal formation has been demonstrated in many types w x of spatial learning tasks 38 , the function of the ventral Ž . hippocampal formation vHF , consisting of the ventral hippocampus proper and the ventral subiculum, is unclear w x 29,38,59 . The topography suggests that ventral subfields should be critical for many non-spatial learning tasks 1 Published on the World Wide Web on 16 November 1999. ) Corresponding author. University of Chicago Medical Center, 5841 South Maryland, MC 3077, Chicago, IL 60637, USA. Tel.: q 1-773-702- 1542; Fax: q 1-708-383-6387; E-mail: m-goldman@uchicago.edu w x 32,38,50,59 , but only minimal supporting evidence for w x this proposition has been provided 38,49 . The hippocampal formation also appears to modulate neuroendocrine, cognitive, and behavioral responses to both learned and some unconditioned psychological stim- w x uli 1,53,56 . Many of these effects appear to be modulated w x by projections from ventral subfields 7,27,33 , and they may offer a more complete accounting of vHF function w x than its putative role in non-spatial learning tasks 38 . Consistent with this concept, are studies demonstrating that the ventral subiculum shortens the time course of hypotha- Ž . Ž lamic-pituitary-adrenal axis HPA activity e.g. plasma . corticosterone in the rat following restraint stress and open-field exposure but not following systemic stimuli Ž . w x e.g. hypoxia or ether exposure 26,28 . Although ventral subicular lesions affected the HPA w x Ž response, ventral hippocampal lesions did not 26 ref. w x . 28 did not address this issue . This is puzzling, because 0006-8993r00r$ - see front matter q 2000 Elsevier Science B.V. All rights reserved. Ž . PII: S0006-8993 99 02281-7