title: Role of the dorsomedial hypothalamus in glucocorticoid-mediated feedback inhibition of the hypothalamic-pituitary-adrenal axis.
abstract: Previous studies suggest that multiple corticolimbic and hypothalamic structures are involved in glucocorticoid-mediated feedback inhibition of the hypothalamic-pituitary-adrenal (HPA) axis, including the dorsomedial hypothalamus (DMH), but a potential role of the DMH has not been directly tested. To investigate the role of the DMH in glucocorticoid-mediated negative feedback, adult male Sprague Dawley rats were implanted with jugular cannulae and bilateral guide cannulae directed at the DMH, and finally were either adrenalectomized (ADX) or were subjected to sham-ADX. ADX rats received corticosterone (CORT) replacement in the drinking water (25 μg/mL), which, based on initial studies, restored a rhythm of plasma CORT concentrations in ADX rats that was similar in period and amplitude to the diurnal rhythm of plasma CORT concentrations in sham-ADX rats, but with a significant phase delay. Following recovery from surgery, rats received microinjections of either CORT (10 ng, 0.5 μL, 0.25 μL/min, per side) or vehicle (aCSF containing 0.2% EtOH), bilaterally, directly into the DMH, prior to a 40-min period of restraint stress. In sham-ADX rats, bilateral intra-DMH microinjections of CORT, relative to bilateral intra-DMH microinjections of vehicle, decreased restraint stress-induced elevation of endogenous plasma CORT concentrations 60 min after the onset of intra-DMH injections. Intra-DMH CORT decreased the overall area under the curve for plasma CORT concentrations during the intermediate time frame of glucocorticoid negative feedback, from 0.5 to 2 h following injection. These data are consistent with the hypothesis that the DMH is involved in feedback inhibition of HPA axis activity at the intermediate time frame.
authors.affiliation: Department of Integrative Physiology and Center for Neuroscience and.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Stamper
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Hennessey
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Hale
authors.forename: Jodi L
authors.initials: JL
authors.lastname: Lukkes
authors.forename: Nina C
authors.initials: NC
authors.lastname: Donner
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Lowe
authors.forename: Evan D
authors.initials: ED
authors.lastname: Paul
authors.forename: Robert L
authors.initials: RL
authors.lastname: Spencer
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Renner
authors.forename: Miles
authors.initials: M
authors.lastname: Orchinik
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Lowry
mesh_terms: D000315:Adrenalectomy; D000818:Animals; D002940:Circadian Rhythm / Q000187:drug effects; D003345:Corticosterone / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004302:Dorsomedial Hypothalamic Nucleus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D025461:Feedback, Physiological; D005938:Glucocorticoids / Q000008:administration & dosage*; D020249:Hormone Replacement Therapy; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical / Q000523:psychology; D015398:Signal Transduction / Q000187:drug effects; D013315:Stress, Psychological / Q000097:blood / Q000503:physiopathology / Q000523:psychology; D013997:Time Factors
chemical_list: D005938:Glucocorticoids; D003345:Corticosterone; D006854:Hydrocortisone
keywords: 5-HT1A; HPA axis; automated blood sampling; corticosterone; dorsomedial hypothalamus; negative feedback; serotonin