Group II metabotropic glutamate receptor type 2 allosteric potentiators prevent sodium lactate-induced panic-like response in panic-vulnerable rats
dc.contributor.author | Johnson, Philip L. | |
dc.contributor.author | Fitz, Stephanie D. | |
dc.contributor.author | Engleman, Eric A. | |
dc.contributor.author | Svensson, Kjell A. | |
dc.contributor.author | Schkeryantz, Jeffrey M. | |
dc.contributor.author | Shekhar, Anantha | |
dc.contributor.department | Department of Anatomy and Cell Biology, IU School of Medicine | en_US |
dc.date.accessioned | 2016-05-06T18:48:23Z | |
dc.date.available | 2016-05-06T18:48:23Z | |
dc.date.issued | 2013-02 | |
dc.description.abstract | Rats 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_US |
dc.eprint.version | Author's manuscript | en_US |
dc.identifier.citation | Johnson, 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/10.1177/0269881112454230 | en_US |
dc.identifier.issn | 1461-7285 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/9557 | |
dc.language.iso | en_US | en_US |
dc.publisher | Sage Publications | en_US |
dc.relation.isversionof | 10.1177/0269881112454230 | en_US |
dc.relation.journal | Journal of Psychopharmacology (Oxford, England) | en_US |
dc.rights | Publisher Policy | en_US |
dc.source | PMC | en_US |
dc.subject | Anti-Anxiety Agents | en_US |
dc.subject | pharmacology | en_US |
dc.subject | Behavior, Animal | en_US |
dc.subject | drug effects | en_US |
dc.subject | Panic | en_US |
dc.subject | Panic Disorder | en_US |
dc.subject | drug therapy | en_US |
dc.subject | Receptors, Metabotropic Glutamate | en_US |
dc.subject | metabolism | en_US |
dc.title | Group II metabotropic glutamate receptor type 2 allosteric potentiators prevent sodium lactate-induced panic-like response in panic-vulnerable rats | en_US |
dc.type | Article | en_US |