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Metabotropic glutamate receptor subtype 7 ablation causes deficit in fear response and conditioned taste aversion.

Metabotropic glutamate receptors (mGluRs) consist of eight different subtypes and exert their effects on second messengers and ion channels via G-proteins. The function of individual mGluR subtypes in the CNS, however, largely remains to be clarified. We examined the fear response of freezing after electric shock in wild-type and mGluR7(-/-) knockout littermates. Wild-type mice displayed freezing immediately after and 1 d after footshock. In comparison, mGluR7(-/-) knockout mice showed significantly reduced levels in both immediate postshock and delayed freezing responses. However, the knockout mice exhibited no abnormalities in pain sensitivity and locomotor activity. To further examine amygdala-dependent behavior, we performed conditioned taste aversion (CTA) experiments. In wild-type mice, the administration of saccharin followed by intraperitoneal injection of the malaise-inducing agent LiCl resulted in an association between saccharin and LiCl. This association caused strong CTA toward saccharin. In contrast, mGluR7(-/-) knockout mice failed to associate between the taste and the negative reinforcer in CTA experiments. Again, the knockout mice showed no abnormalities in taste preference and in the sensitivity to LiCl toxicity. These results indicate that mGluR7 deficiency causes an impairment of two distinct amygdala-dependent behavioral paradigms. Immunohistochemical and immunoelectron-microscopic analyses showed that mGluR7 is highly expressed in amygdala and preferentially localized at the presynaptic axon terminals of glutamatergic neurons. Together, these findings strongly suggest that mGluR7 is involved in neural processes subserving amygdala-dependent averse responses.

Pubmed ID: 9920659


  • Masugi M
  • Yokoi M
  • Shigemoto R
  • Muguruma K
  • Watanabe Y
  • Sansig G
  • van der Putten H
  • Nakanishi S


The Journal of neuroscience : the official journal of the Society for Neuroscience

Publication Data

February 1, 1999

Associated Grants


Mesh Terms

  • Animals
  • Avoidance Learning
  • Conditioning (Psychology)
  • Fear
  • Mice
  • Mice, Knockout
  • Presynaptic Terminals
  • Receptors, Metabotropic Glutamate
  • Taste