title: Cardiac arrest and cardiopulmonary resuscitation dysregulates the hypothalamic-pituitary-adrenal axis.
abstract: Cardiac arrest and cardiopulmonary resuscitation (CA/CPR) increase the risk for affective disorders in human survivors. Postischemic anxiety- and depressive-like behaviors have been documented in animal models of CA/CPR; however, the stability of post-CA/CPR anxiety-like behavior over time and the underlying physiologic mechanisms remain unknown. The hypothalamic-pituitary-adrenal (HPA) axis and the corticotropin releasing factor (CRF) system may mediate the pathophysiology of anxiety and depression; therefore, this study measured CA/CPR-induced changes in CRF receptor binding and HPA axis negative feedback. Mice were exposed to CA/CPR or SHAM surgery and assessed 7 or 21 days later. Consistent with earlier demonstrations of anxiety-like behavior 7 days after CA/CPR, increased anxiety-like behavior in the open field was also present 21 days after CA/CPR. On postoperative day 7, CA/CPR was associated with an increase in basal serum corticosterone concentration relative to SHAM, but this difference resolved by postoperative day 21. The Dexamethasone Suppression Test showed that the CA/CPR group had enhanced negative feedback compared with SHAM controls at postoperative day 21. Furthermore, there was a gradual increase in CRF(1) receptor binding in the paraventricular nucleus of the hypothalamus and bed nucleus of the stria terminalis, as well as a transient decrease of both CRF(1) and CRF(2A) receptors in the dorsal hippocampus. Therefore, sustained changes in activity of the HPA axis and the CRF system after CA/CPR may contribute to the postischemic increase in affective disorders.
authors: Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia 30322, USA. gretchen.neigh@emory.edu
authors: Gretchen N
authors: GN
authors: Neigh
authors: Kate
authors: K
authors: Karelina
authors: Ning
authors: N
authors: Zhang
authors: Erica R
authors: ER
authors: Glasper
authors: Michael J
authors: MJ
authors: Owens
authors: Paul M
authors: PM
authors: Plotsky
authors: Charles B
authors: CB
authors: Nemeroff
authors: A Courtney
authors: AC
authors: Devries
mesh_terms: D000818:Animals; D001007:Anxiety; D016887:Cardiopulmonary Resuscitation / Q000009:adverse effects*; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone; D006323:Heart Arrest / Q000150:complications* / Q000628:therapy; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D007031:Hypothalamus; D051379:Mice; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D018019:Receptors, Corticotropin-Releasing Hormone / Q000032:analysis / Q000378:metabolism; D013997:Time Factors; D000099052:CRF Receptor, Type 1
chemical_list: C101531:CRF receptor type 2; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone