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

Metabotropic glutamate receptors (mGluRs) consist of eight different subtyp es and exert their effects on second messengers and ion channels via G-prot eins. The function of individual mGluR subtypes in the CNS, however, largel y 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 comp arison, 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 t aste aversion (CTA) experiments. In wild-type mice, the administration of s accharin followed by intraperitoneal injection of the malaise-inducing agen t LiCl resulted in an association between saccharin and LiCl. This associat ion 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-depend ent behavioral paradigms. Immunohistochemical and immunoelectron-microscopi c analyses showed that mGluR7 is highly expressed in amygdala and preferent ially localized at the presynaptic axon terminals of glutamatergic neurons. Together, these findings strongly suggest that mGluR7 is involved in neura l processes subserving amygdala-dependent averse responses.