Stamper Christopher E, Hennessey Patrick A, Hale Matthew W, Lukkes Jodi L, Donner Nina C, Lowe Kenneth R, Paul Evan D, Spencer Robert L, Renner Kenneth J, Orchinik Miles, Lowry Christopher A
Department of Integrative Physiology and Center for Neuroscience and.
Stress. 2015 Jan;18(1):76-87. doi: 10.3109/10253890.2015.1004537. Epub 2015 Feb 17.
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.
先前的研究表明，多个皮质边缘和下丘脑结构参与了糖皮质激素介导的下丘脑-垂体-肾上腺（HPA）轴的反馈抑制，包括背内侧下丘脑（DMH），但DMH的潜在作用尚未得到直接验证。为了研究DMH在糖皮质激素介导的负反馈中的作用，成年雄性Sprague Dawley大鼠植入颈静脉插管和双侧指向DMH的引导插管，最后进行肾上腺切除术（ADX）或假手术。ADX大鼠在饮用水中接受皮质酮（CORT）替代（25μg/mL），根据初步研究，这恢复了ADX大鼠血浆CORT浓度的节律，其周期和幅度与假手术大鼠血浆CORT浓度的昼夜节律相似，但有明显的相位延迟。手术后恢复后，在40分钟的束缚应激前，大鼠双侧直接向DMH内微量注射CORT（10 ng，0.5μL，0.25μL/分钟，每侧）或溶剂（含0.2%乙醇的人工脑脊液）。在假手术大鼠中，相对于双侧DMH内微量注射溶剂，双侧DMH内微量注射CORT可降低DMH内注射开始60分钟后束缚应激诱导的内源性血浆CORT浓度升高。DMH内注射CORT降低了糖皮质激素负反馈中间时间段（注射后0.5至2小时）血浆CORT浓度曲线下的总面积。这些数据与DMH在中间时间段参与HPA轴活动的反馈抑制这一假设一致。
