1. ¹Neuroscience Research, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland
2. ²Tierphysiologie, Zoologisches Institut, Fakultät für Biologie, Universität Tübingen, Tübingen, Germany
3. ³Genome and Proteome Sciences, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland

Correspondence: Dr JF Cryan, Department of Pharmacology & Therapeutics, School of Pharmacy, University College Cork, Cork, Ireland. E-mail: j.cryan@ucc.ie; Dr PJ Flor, Neuroscience Research, Novartis Institutes for BioMedical Research, Novartis Pharma AG, CH-4002 Basel, Switzerland. E-mail: peter_josef.flor@novartis.com

⁴These authors contributed equally to this work.

⁵Current address: Biosciences R&D, Science & Technology, Medtronic Inc., Minneapolis, MN, USA.

Received 1 November 2006; Revised 20 May 2007; Accepted 6 June 2007; Published online 21 August 2007.

Abstract

Formation and extinction of aversive memories in the mammalian brain are insufficiently understood at the cellular and molecular levels. Using the novel metabotropic glutamate receptor 7 (mGluR7) agonist AMN082, we demonstrate that mGluR7 activation facilitates the extinction of aversive memories in two different amygdala-dependent tasks. Conversely, mGluR7 knockdown using short interfering RNA attenuated the extinction of learned aversion. mGluR7 activation also blocked the acquisition of Pavlovian fear learning and its electrophysiological correlate long-term potentiation in the amygdala. The finding that mGluR7 critically regulates extinction, in addition to acquisition of aversive memories, demonstrates that this receptor may be relevant for the manifestation and treatment of anxiety disorders.