Shekhar, AnanthaJohnson, Philip L.Sajdyk, Tammy J.Fitz, Stephanie D.Keim, Stanley R.Kelley, Pamela E.Gehlert, Donald R.DiMicco, Joseph A.2019-10-162019-10-162006-09-06Shekhar, A., Johnson, P. L., Sajdyk, T. J., Fitz, S. D., Keim, S. R., Kelley, P. E., … DiMicco, J. A. (2006). Angiotensin-II is a putative neurotransmitter in lactate-induced panic-like responses in rats with disruption of GABAergic inhibition in the dorsomedial hypothalamus. The Journal of neuroscience : the official journal of the Society for Neuroscience, 26(36), 9205–9215. doi:10.1523/JNEUROSCI.2491-06.2006https://hdl.handle.net/1805/21180Intravenous sodium lactate infusions or the noradrenergic agent yohimbine reliably induce panic attacks in humans with panic disorder but not in healthy controls. However, the exact mechanism of lactate eliciting a panic attack is still unknown. In rats with chronic disruption of GABA-mediated inhibition in the dorsomedial hypothalamus (DMH), achieved by chronic microinfusion of the glutamic acid decarboxylase inhibitor L-allylglycine, sodium lactate infusions or yohimbine elicits panic-like responses (i.e., anxiety, tachycardia, hypertension, and tachypnea). In the present study, previous injections of the angiotensin-II (A-II) type 1 receptor antagonist losartan and the nonspecific A-II receptor antagonist saralasin into the DMH of "panic-prone" rats blocked the anxiety-like and physiological components of lactate-induced panic-like responses. In addition, direct injections of A-II into the DMH of these panic-prone rats also elicited panic-like responses that were blocked by pretreatment with saralasin. Microinjections of saralasin into the DMH did not block the panic-like responses elicited by intravenous infusions of the noradrenergic agent yohimbine or by direct injections of NMDA into the DMH. The presence of the A-II type 1 receptors in the region of the DMH was demonstrated using immunohistochemistry. Thus, these results implicate A-II pathways and the A-II receptors in the hypothalamus as putative substrates for sodium lactate-induced panic-like responses in vulnerable subjects.en-USPublisher PolicyAnxietyCircumventricular organsGABAMedial preoptic nucleusOrganum vasculosum lamina terminalisSaralasinStressSubfornical organLosartanAT1 receptorArticle