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Neuropharmacology. 2013 Mar;66:365-72. doi: 10.1016/j.neuropharm.2012.07.038. Epub 2012 Aug 2.

Role of mGluR4 in acquisition of fear learning and memory.

Author information

1
Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA.

Abstract

Group III metabotropic glutamate receptors (mGluRs), which are generally located presynaptically, modulate synaptic transmission by regulating neurotransmitter release. Previously we showed enhanced amygdala-dependent cued fear conditioning in mGluR4(-/-) mice 24 h following training involving two tone-shock pairings. In this study, we assessed the effects of modulating mGluR4 signaling on acquisition and extinction of conditioned fear. mGluR4(-/-) and wild-type female and male mice received 10 tone-shock pairings during training. Compared to wild-type mice, mGluR4(-/-) mice showed enhanced acquisition and extinction of cued fear. Next, we assessed whether acute pharmacological stimulation of mGluR4 with the specific orthosteric mGluR4 agonist LSP1-2111 also affects acquisition and extinction of cued fear. Consistent with the enhanced acquisition of cued fear in mGluR4(-/-), LSP1-2111, at 2.5 and 5 mg/kg, inhibited acquisition of cued fear conditioning in wild-type male mice. The drug's effect on extinction was less clear and only a subtle effect was seen at 5 mg/kg. Finally, analysis of microarray data of amygdala tissues from mGluR4(-/-) versus wild-type and from wild-type mice treated with a mGluR4 agonist versus saline revealed a significant overlap in pattern of gene expression. Together, these data support a role for mGluR4 signaling in acquisition of fear learning and memory. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'.

PMID:
22884897
PMCID:
PMC3508079
DOI:
10.1016/j.neuropharm.2012.07.038
[Indexed for MEDLINE]
Free PMC Article

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