title: Chronic salt-loading reduces basal excitatory input to CRH neurons in the paraventricular nucleus and accelerates recovery from restraint stress in male mice.
abstract: Neurons synthesizing corticotrophin-releasing hormone (CRH) in the paraventricular nucleus of the hypothalamus (PVN) are activated during acute stress and act via the hypothalamic-pituitary-adrenal (HPA) axis to increase systemic levels of corticosterone (CORT). Recent data indicates that CRH neurons in the PVN are inhibited by acute salt-loading, and that this inhibition blunts the response to restraint stress as measured by increases in plasma CORT. The current study evaluates the effects of chronic rather than acute salt-loading on stress-induced activation of the HPA axis. Relative to euhydrated controls, chronic salt-loading over a 5-day period elevated plasma sodium and fluid intake without eliciting hypovolemia or substantial alterations in food intake or body weight. Chronic salt-loading also decreased expression of CRH mRNA in the anterior but not posterior portion of the PVN. Similarly, whole cell patch clamp recordings revealed that salt-loading effectively decreases spontaneous excitatory input to CRH neurons in the PVN without altering spontaneous inhibitory input. Generally consistent with these observations, chronic salt attenuated HPA axis activation as indicated by a significant reduction of plasma CORT during recovery from restraint stress.
authors.affiliation: Department of Pharmacodynamics, College of Pharmacy, University of Florida, United States.
authors.forename: Eric G
authors.initials: EG
authors.lastname: Krause
authors.affiliation: Department of Pharmacodynamics, College of Pharmacy, University of Florida, United States.
authors.forename: Dipanwita
authors.initials: D
authors.lastname: Pati
authors.affiliation: Department of Pharmacodynamics, College of Pharmacy, University of Florida, United States; Department of Neuroscience, College of Medicine, University of Florida, United States. Electronic address: cjfraz@ufl.edu.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Frazier
mesh_terms: D000818:Animals; D019540:Area Under Curve; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D004326:Drinking / Q000187:drug effects; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology*; D018408:Patch-Clamp Techniques; D011810:Quinoxalines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D020127:Recovery of Function / Q000187:drug effects*; D012149:Restraint, Physical; D012492:Salts / Q000494:pharmacology*; D012964:Sodium / Q000097:blood; D013997:Time Factors; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D008164:Luminescent Proteins; D011810:Quinoxalines; D012333:RNA, Messenger; D012492:Salts; C056723:FG 9041; C056639:2-amino-5-phosphopentanoic acid; D003346:Corticotropin-Releasing Hormone; D012964:Sodium; D014633:Valine