GluR7 facilitates extinction of aversive memories and controls amygdala plasticity. Mol Psychiatry

Neuroscience Research, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland.
Molecular Psychiatry (Impact Factor: 14.5). 09/2007; 13(10):970-9. DOI: 10.1038/
Source: PubMed


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.

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Available from: Peter J Flor
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    • "mGluR7 is a member of the most evolutionarily conserved group III mGluRs and plays a key role in brain and synaptic function. Studies from mGluR7-deficient and siRNA knockdown animals displayed deficits in fear learning, aversive behavior, stress response, and working memory, supporting the key role in brain physiology [Masugi et al., 1999; Cryan et al., 2003; Callaerts-Vegh et al., 2006; Fendt et al., 2008; O'Connor et al., 2012; Fendt et al., 2013]. At the synaptic level, it appears to modulate presynaptic neurotransmitter of Gamma Amino Acid Butyric Acid (GABA) and L-glutamate as well as postsynaptic N-methyl-D-aspartic acid receptors (NMDARs), thereby contributing to different emotional status such as anxiety, depression, and cognitive dysfunction [O'Connor et al., 2010; Nicoletti et al., 2011; Gee et al., 2014]. "
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    • "istration are described ( Bahi et al . , 2012 ; Cleva et al . , 2012 ) . Activation of mGlu 7 receptors in the amygdala and the periaqueductal gray by AMN082 augments nocicep - tive behavior ( Marabese et al . , 2007 ) . Furthermore , AMN082 prevented the acquisition of fear learning , facilitated fear extinction and impaired LTP in the amygdala ( Fendt et al . , 2008 ) . Interestingly , unlike MAP4 , MPPG and MSOP , MMPIP ( a selective receptor mGlu 7 antagonist ) did not show proconvulsant activity in rodents ( Flor & Acher , 2012 ) . 2 . 3 . 5 . 5 . mGlu 7 receptors and drugs of abuse . Very recent animal findings point a specific influence of tonic activation of mGlu 7 receptors in drug addiction"
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    • "This dose of DMSO is not known to produce toxic effects [52]. The AMN082 doses were based on previous studies using AMN082 effectively in amygdala-dependent associative learning tasks [36] "
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