title: Metabotropic glutamate2/3 receptor agonism facilitates autonomic recovery after pharmacological panic challenge in healthy humans.
abstract: Group II metabotropic glutamate receptors (mGluR2/3) are suggested to modulate anxiety, arousal, and stress including autonomic control. However, no study has investigated mGluR2/3-related effects on baseline autonomic activity and reactivity to emotional challenge in humans as yet. Using a double-blind, randomized placebo-controlled, cross-over study design, we investigated the influence of a 1-week treatment with the mGluR2/3 agonist LY544344, prodrug of LY354740, on autonomic reactivity to a cholecystokinin tetrapeptide (CCK-4) panic challenge in eight healthy young men. The main outcome measures were time and frequency domain heart rate variability parameters during baseline, CCK-4 challenge, and recovery. There was no evidence for LY544344-mediated effects on baseline and CCK-4 challenge vagal activity, but a significantly lower recovery low frequency (%) and low frequency/high frequency ratio in the LY544344 group, suggesting enhanced autonomic recovery. This pilot study provides first human data indicating that mGluR2/3 agonism is involved in autonomic responsiveness, suggesting an important role of mGluR2/3 in central autonomic regulation.
authors.affiliation: Departments of aPsychiatry and Psychotherapy bPsychosomatic Medicine and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Departments of cFunctional Genomics dMolecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Agorastos
authors.initials: A
authors.lastname: Agorastos
authors.forename: Cüneyt
authors.initials: C
authors.lastname: Demiralay
authors.forename: Oliver
authors.initials: O
authors.lastname: Stiedl
authors.forename: Christoph
authors.initials: C
authors.lastname: Muhtz
authors.forename: Klaus
authors.initials: K
authors.lastname: Wiedemann
authors.forename: Michael
authors.initials: M
authors.lastname: Kellner
mesh_terms: D000328:Adult; D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D064368:Healthy Volunteers; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D010200:Panic / Q000187:drug effects*; D010865:Pilot Projects; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D013758:Tetragastrin / Q000494:pharmacology*; D055815:Young Adult
chemical_list: C503966:2-((2'-amino)propionyl)aminobicyclo(3.1.0)hexane-2,6-dicarboxylic acid; D001643:Bridged Bicyclo Compounds; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; D013758:Tetragastrin; D000409:Alanine