Johnson, Philip L.Fitz, Stephanie D.Engleman, Eric A.Svensson, Kjell A.Schkeryantz, Jeffrey M.Shekhar, Anantha2016-05-062016-05-062013-02Johnson, P. L., Fitz, S. D., Engleman, E. A., Svensson, K. A., Schkeryantz, J. M., & Shekhar, A. (2013). Group II metabotropic glutamate receptor type 2 allosteric potentiators prevent sodium lactate-induced panic-like response in panic-vulnerable rats. Journal of Psychopharmacology (Oxford, England), 27(2), 152–161. http://doi.org/10.1177/02698811124542301461-7285https://hdl.handle.net/1805/9557Rats with chronic inhibition of GABA synthesis by infusion of l-allyglycine, a glutamic acid decarboxylase inhibitor, into their dorsomedial/perifornical hypothalamus are anxious and exhibit panic-like cardio-respiratory responses to treatment with intravenous (i.v.) sodium lactate (NaLac) infusions, in a manner similar to what occurs in patients with panic disorder. We previously showed that either NMDA receptor antagonists or metabotropic glutamate receptor type 2/3 receptor agonists can block such a NaLac response, suggesting that a glutamate mechanism is contributing to this panic-like state. Using this animal model of panic, we tested the efficacy of CBiPES and THIIC, which are selective group II metabotropic glutamate type 2 receptor allosteric potentiators (at 10-30 mg/kg i.p.), in preventing NaLac-induced panic-like behavioral and cardiovascular responses. The positive control was alprazolam (3mg/kg i.p.), a clinically effective anti-panic benzodiazepine. As predicted, panic-prone rats given a NaLac challenge displayed NaLac-induced panic-like cardiovascular (i.e. tachycardia and hypertensive) responses and "anxiety" (i.e. decreased social interaction time) and "flight" (i.e. increased locomotion) -associated behaviors; however, systemic injection of the panic-prone rats with CBiPES, THIIC or alprazolam prior to the NaLac dose blocked all NaLac-induced panic-like behaviors and cardiovascular responses. These data suggested that in a rat animal model, selective group II metabotropic glutamate type 2 receptor allosteric potentiators show an anti-panic efficacy similar to alprazolam.en-USPublisher PolicyAnti-Anxiety AgentspharmacologyBehavior, Animaldrug effectsPanicPanic Disorderdrug therapyReceptors, Metabotropic GlutamatemetabolismArticle