{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:49:24Z","timestamp":1791265764817,"version":"4.1.0"},"reference-count":65,"publisher":"S. Karger AG","issue":"2","license":[{"start":{"date-parts":[[2016,4,15]],"date-time":"2016-04-15T00:00:00Z","timestamp":1460678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2016,4,15]],"date-time":"2016-04-15T00:00:00Z","timestamp":1460678400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuroendocrinology"],"published-print":{"date-parts":[[2017]]},"abstract":"<jats:p>&lt;b&gt;&lt;i&gt;Introduction:&lt;\/i&gt;&lt;\/b&gt; Prolonged and repeated stresses cause hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. The corticotrophin-releasing hormone (CRH)-expressing neurons in the hypothalamic paraventricular nucleus (PVN) are an essential component of the HPA axis. &lt;b&gt;&lt;i&gt;Materials and Methods:&lt;\/i&gt;&lt;\/b&gt; Chronic unpredictable mild stress (CUMS) was induced in Sprague-Dawley rats. GABA reversal potentials (E&lt;sub&gt;GABA&lt;\/sub&gt;) were determined by using gramicidin-perforated recordings in identified PVN-CRH neurons through expressing enhanced green fluorescent protein driven by the CRH promoter. Plasma corticosterone (CORT) levels were measured in rats implanted with a cannula targeting the lateral ventricles and PVN. &lt;b&gt;&lt;i&gt;Results:&lt;\/i&gt;&lt;\/b&gt; Blocking the GABA&lt;sub&gt;A&lt;\/sub&gt; receptor in the PVN with gabazine significantly increased plasma CORT levels in unstressed rats but did not change CORT levels in CUMS rats. CUMS caused a depolarizing shift in E&lt;sub&gt;GABA&lt;\/sub&gt; in PVN-CRH neurons compared with E&lt;sub&gt;GABA&lt;\/sub&gt; in PVN-CRH neurons in unstressed rats. Furthermore, CUMS induced a long-lasting increase in expression levels of the cation chloride cotransporter Na&lt;sup&gt;+&lt;\/sup&gt;-K&lt;sup&gt;+&lt;\/sup&gt;-Cl&lt;sup&gt;-&lt;\/sup&gt;-Cl&lt;sup&gt;-&lt;\/sup&gt; (NKCC1) in the PVN but a transient decrease in expression levels of K&lt;sup&gt;+&lt;\/sup&gt;-Cl&lt;sup&gt;-&lt;\/sup&gt;-Cl&lt;sup&gt;-&lt;\/sup&gt; in the PVN, which returned to the basal level 5 days after CUMS treatment. The NKCC1 inhibitor bumetanide decreased the basal firing activity of PVN-CRH neurons and normalized E&lt;sub&gt;GABA&lt;\/sub&gt; and the gabazine-induced excitatory effect on PVN-CRH neurons in CUMS rats. In addition, central administration of bumetanide decreased basal circulating CORT levels in CUMS rats. &lt;b&gt;&lt;i&gt;Conclusions:&lt;\/i&gt;&lt;\/b&gt; These data suggest that chronic stress impairs GABAergic inhibition, resulting in HPA axis hyperactivity through upregulation of NKCC1.<\/jats:p>","DOI":"10.1159\/000446114","type":"journal-article","created":{"date-parts":[[2016,4,14]],"date-time":"2016-04-14T21:03:19Z","timestamp":1460667799000},"page":"194-208","source":"Crossref","is-referenced-by-count":57,"title":["Chronic Unpredictable Mild Stress Induces Loss of GABA Inhibition in Corticotrophin-Releasing Hormone-Expressing Neurons through NKCC1 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