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'.
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Authors | Matthew J Davis, Ovidiu D Iancu, Francine C Acher, Blair M Stewart, Massarra A Eiwaz, Robert M Duvoisin, Jacob Raber |
Journal | Neuropharmacology
(Neuropharmacology)
Vol. 66
Pg. 365-72
(Mar 2013)
ISSN: 1873-7064 [Electronic] England |
PMID | 22884897
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2012 Elsevier Ltd. All rights reserved. |
Chemical References |
- Aminobutyrates
- Excitatory Amino Acid Agonists
- LSP1 2111
- Phosphinic Acids
- Receptors, Metabotropic Glutamate
- metabotropic glutamate receptor 4
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Topics |
- Aminobutyrates
(pharmacology)
- Amygdala
(drug effects, physiology)
- Animals
- Conditioning, Psychological
(drug effects, physiology)
- Excitatory Amino Acid Agonists
(pharmacology)
- Extinction, Psychological
(drug effects, physiology)
- Fear
(drug effects, physiology)
- Female
- Gene Expression
(drug effects, physiology)
- Male
- Memory
(drug effects, physiology)
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Phosphinic Acids
(pharmacology)
- Receptors, Metabotropic Glutamate
(agonists, genetics, physiology)
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