EMPIRICAL PAPERSSelective activation of metabotropic G-protein-coupled glutamate 7 receptor elicits anxiolytic-like effects in mice by modulating GABAergic neurotransmissionStachowicz, Katarzynaa; Brañski, Piotra; Kłak, Kingaa; van der Putten, Hermanb; Cryan, John F.b; Flor, Peter J.b; Andrzej, Pilca cAuthor Information aInstitute of Pharmacology, Polish Academy of Sciences, Smêtna bNeuroscience Research, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland cCollegium Medicum, Jagiellonian University, Kraków, Poland Correspondence to Professor Pilc Andrzej, MD, PhD, Institute of Pharmacology, Polish Academy of Sciences, Smêtna 12, 31-343 Krakow, Poland E-mail: email@example.com Received 12 March 2008 Accepted as revised 23 May 2008 Behavioural Pharmacology: September 2008 - Volume 19 - Issue 5-6 - p 597-603 doi: 10.1097/FBP.0b013e32830cd839 Buy Metrics Abstract We describe the anxiolytic-like effects of the first, selective metabotropic G-protein-coupled glutamate 7 (mGlu7) receptor agonist, N,N′-dibenzyhydryl-ethane-1,2-diamine dihydrochloride (AMN082), as measured in the modified stress-induced hyperthermia (SIH) and the four-plate tests. Administration of AMN082 (3–6 mg/kg intraperitoneally) to Swiss mice produced anxiolytic-like effects in the modified SIH and four-plate tests. Moreover, it was ineffective as an anxiolytic in the SIH test in mGlu7 receptor knockout mice as compared with wild-type C57BL/6J littermate controls. In contrast, diazepam (1.25–5 mg/kg) significantly reduced SIH in both the wild-type and knockout animals. The anxiolytic-like effect of AMN082 in the SIH paradigm was abolished by pretreatment with flumazenil (10 mg/kg intraperitoneally). This indicates an involvement of γ-aminobutyric acid-ergic neurotransmission in AMN's anxiolytic actions. The results indicate that activation of the mGlu7 receptor produces anxiolytic-like effects via the modulation of the γ-aminobutyric acid system. © 2008 Lippincott Williams & Wilkins, Inc.