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Neurosci."],"published-print":{"date-parts":[[2006,6,28]]},"abstract":"<jats:p>Rats with chronic inhibition of GABA synthesis and consequently enhanced glutamatergic excitation in the dorsomedial hypothalamus (DMH) develop panic-like responses, defined as tachycardia, tachypnea, hypertension, and increased anxiety as measured by a social interaction (SI) test, after intravenous sodium lactate infusions, a phenomenon similar to patients with panic disorder. Therefore, the present studies tested the role of the postsynaptic NMDA and AMPA type glutamatergic receptors in the lactate-induced panic-like responses in these rats. Rats were fit with femoral arterial and venous catheters and Alzet pumps [filled with the GABA synthesis inhibitor<jats:sc>l<\/jats:sc>-allylglycine (<jats:sc>l<\/jats:sc>-AG; 3.5 nmol\/0.5 \u03bcl per hour) or its inactive isomer<jats:sc>d<\/jats:sc>-AG] into the DMH. After 4\u20135 d of recovery only those rats with<jats:sc>l<\/jats:sc>-AG pumps exhibited panic-like responses to lactate infusions. Using double immunocytochemistry, we found that rats exhibiting panic-like responses (e.g.,<jats:sc>l<\/jats:sc>-AG plus lactate) had increased c-Fos immunoreactivity in DMH neurons expressing the NMDA receptor 1 (NR1) subunit, but not those expressing the glutamate receptor 2 and 3 subunits of the AMPA receptors. To confirm this pharmacologically, we tested another group of rats implanted with<jats:sc>l<\/jats:sc>-AG pumps with intravenous lactate infusions preceded by injections of either NMDA [aminophosphonopentanoic acid (AP-5) or (+)-5-methyl-10,11-dihydro-<jats:sup>5<\/jats:sup><jats:italic>H<\/jats:italic>-dibenzo [a,d]cyclohepten-5,10-imine maleate (MK-801)] or non-NMDA [CNQX or 4-(8-methyl-<jats:sup>9<\/jats:sup><jats:italic>H<\/jats:italic>-1,3-dioxolo[4,5-h][2,3]benzodazepin-5-yl)-benzenamine dihydrochloride (GYKI52466)] antagonists into the DMH. Injections of NMDA, but not non-NMDA, antagonists into the DMH resulted in dose-dependent blockade of the tachycardia, tachypnea, hypertension, and SI responses after lactate infusions. These results suggest that NMDA, and not non-NMDA, type glutamate receptors regulate lactate-induced panic-like responses in rats with GABA dysfunction in the DMH.<\/jats:p>","DOI":"10.1523\/jneurosci.0408-06.2006","type":"journal-article","created":{"date-parts":[[2006,6,28]],"date-time":"2006-06-28T17:16:54Z","timestamp":1151515014000},"page":"7093-7104","source":"Crossref","is-referenced-by-count":80,"title":["Panic-Prone State Induced in Rats with GABA Dysfunction in the Dorsomedial Hypothalamus Is Mediated by NMDA Receptors"],"prefix":"10.1523","volume":"26","author":[{"given":"Philip L.","family":"Johnson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anantha","family":"Shekhar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"393","published-online":{"date-parts":[[2006,6,28]]},"reference":[{"key":"2023041303191124000_26.26.7093.1","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3908(88)90013-5"},{"key":"2023041303191124000_26.26.7093.2","doi-asserted-by":"crossref","first-page":"R8","DOI":"10.1152\/ajpregu.2001.280.1.R8","volume":"280","year":"(2001)","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"2023041303191124000_26.26.7093.3","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(03)03047-6"},{"key":"2023041303191124000_26.26.7093.4","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1152\/ajplegacy.1928.84.3.490","volume":"84","year":"(1928)","journal-title":"Am J Physiol"},{"key":"2023041303191124000_26.26.7093.5","first-page":"362","volume":"27","year":"(1948)","journal-title":"Res Publ Assoc Res Nerv Ment Dis"},{"key":"2023041303191124000_26.26.7093.6","doi-asserted-by":"crossref","unstructured":"Bernardis LL, Bellinger LL (1998) The dorsomedial hypothalamic nucleus revisited: 1998 update. 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