Neonatal lesions of the ventral hippocampal formation disrupt neuroendocrine responses to auditory stress in the adult rat.
Lesioning the ventral hippocampal formation (vHF) in the neonatal rat with an excitotoxin replicates several features of schizophrenia. Similar lesions in the adult rat disrupt the normal constraint of neuroendocrine responses to environmental stressors, which is of potential interest because the enhanced HPA axis and antidiuretic hormone activity in schizophrenia is linked to acute stress and hippocampal formation (HF) pathology. In the current study, we investigated the effects of neonatal ventral hippocampal formation lesions (NVHFL) on plasma adrenocorticotropin hormone (ACTH) and arginine vasopressin (AVP) responses following a 2-min acoustic stressor in the adult rat. Levels of the two hormones did not differ between SHAM-operated and NVHFL animals in their home cages. ACTH levels doubled in SHAM-operated animals immediately following stress, but increased more than six-fold in the NVHFL group. AVP levels were halved immediately following stress in SHAM-operated animals, but did not change significantly in NVHFL. Findings could not be attributed to intervening factors known to influence neuroendocrine activity. Thus, NVHFL appear to disrupt the HF-mediated constraint of neuroendocrine responses to stress, and model the neuroendocrine dysfunction seen in schizophrenia. We posit that clarification of how NVHFL alters relatively "simple", well characterized, and phylogenetically preserved systems, such as the neuroendocrine system, may provide insight into the mechanism of hippocampal pathology in schizophrenia.
Psychiatric Institute, University of Illinois in Affiliation with University of Chicago, 1601 W. Taylor, Chicago, IL 60612, USA.
Colin P
CP
Mitchell
Morris B
MB
Goldman
D000161:Acoustic Stimulation; D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D003345:Corticosterone / Q000097:blood; D004195:Disease Models, Animal; D006624:Hippocampus / Q000502:physiology*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D008297:Male; D010913:Pituitary-Adrenal System / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000502:physiology; D012559:Schizophrenia / Q000503:physiopathology; D013315:Stress, Psychological / Q000097:blood*; D014668:Vasotocin / Q000097:blood*
D000324:Adrenocorticotropic Hormone; D014668:Vasotocin; D003345:Corticosterone