Glucocorticoid receptors in the nucleus of the solitary tract (NTS) decrease endocrine and behavioral stress responses.
Stress activates the hypothalamo-pituitary-adrenal (HPA) axis, leading to adrenocortical secretion of glucocorticoids. The magnitude and duration of the HPA axis response is mediated in large part by the glucocorticoid receptor (GR). The nucleus of the solitary tract (NTS) abundantly expresses the GR and is a key brain region for processing autonomic and endocrine stress responses. This study tests the hypothesis that GR within the NTS plays an important role in inhibiting stress-induced endocrine and behavioral responses. Cohorts of rats received bilateral micropellet (30 μg) implantations of crystalline corticosterone, mifepristone (a GR antagonist) or cholesterol (control) directed into the region of the NTS, and were subsequently subjected to either acute psychogenic (restraint) stress or chronic variable stress (CVS). We found that NTS GR antagonism increased acute stress-induced corticosterone levels, whereas GR activation within the NTS attenuated this response. Following CVS, basal and 15 min post-restraint plasma corticosterone levels were increased by NTS GR antagonism, which was associated with an increase in Fos immunoreactivity within the PVN. Using the elevated plus maze (EPM) and forced swim test (FST), we assessed the effect of NTS GR inhibition on anxiety- and depression-like behaviors, respectively. GR inhibition within the NTS decreased open arm exploratory behavior in the EPM and increased immobility in the FST relative to controls. Together, the findings reveal a novel role of NTS GR signaling for inhibiting both endocrine and behavioral responses to stress.
Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati Metabolic Diseases Institute, Cincinnati, OH 45237, United States. Electronic address: ghosalsa@mail.uc.edu.
Sriparna
S
Ghosal
Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati Metabolic Diseases Institute, Cincinnati, OH 45237, United States.
Jana
J
Bundzikova-Osacka
Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati Metabolic Diseases Institute, Cincinnati, OH 45237, United States.
C Mark
CM
Dolgas
Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati Metabolic Diseases Institute, Cincinnati, OH 45237, United States.
Brent
B
Myers
Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati Metabolic Diseases Institute, Cincinnati, OH 45237, United States.
James P
JP
Herman
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D003345:Corticosterone / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D004343:Drug Implants; D006728:Hormones / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D015735:Mifepristone / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000819:agonists / Q000502:physiology*; D017552:Solitary Nucleus / Q000187:drug effects / Q000378:metabolism*; D013315:Stress, Psychological / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control
D004343:Drug Implants; D006728:Hormones; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D003345:Corticosterone
Chronic stress; Chronic variable stress; Corticosterone; Depression; HPA axis