Group II metabotropic glutamate receptor type 2 allosteric potentiators prevent sodium lactate-induced panic-like response in panic-vulnerable rats
| Autor: | Philip L. Johnson, Anantha Shekhar, Eric A. Engleman, Jeffrey M. Schkeryantz, Stephanie D. Fitz, Kjell Svensson |
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| Rok vydání: | 2012 |
| Předmět: |
Male
medicine.medical_specialty CBiPES Glutamate decarboxylase Glutamic Acid Anxiety Pharmacology Receptors Metabotropic Glutamate Cardiovascular System behavioral disciplines and activities Article Rats Sprague-Dawley Sodium Lactate Internal medicine mental disorders medicine Animals Pharmacology (medical) gamma-Aminobutyric Acid Alprazolam Behavior Animal business.industry Glutamate receptor Glutamic acid Panic Rats Psychiatry and Mental health Endocrinology Metabotropic receptor Anti-Anxiety Agents Metabotropic glutamate receptor Panic Disorder NMDA receptor business medicine.drug |
| Zdroj: | Journal of Psychopharmacology. 27:152-161 |
| ISSN: | 1461-7285 0269-8811 |
| Popis: | 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 10–30mg/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. |
| Databáze: | OpenAIRE |
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