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Role of mGluR4 in acquisition of fear learning and memory.
- Source :
-
Neuropharmacology [Neuropharmacology] 2013 Mar; Vol. 66, pp. 365-72. Date of Electronic Publication: 2012 Aug 02. - Publication Year :
- 2013
-
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'.<br /> (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Subjects :
- Aminobutyrates pharmacology
Amygdala drug effects
Amygdala physiology
Animals
Conditioning, Psychological drug effects
Excitatory Amino Acid Agonists pharmacology
Extinction, Psychological drug effects
Extinction, Psychological physiology
Fear drug effects
Female
Gene Expression drug effects
Gene Expression physiology
Male
Memory drug effects
Mice
Mice, Inbred C57BL
Mice, Knockout
Phosphinic Acids pharmacology
Receptors, Metabotropic Glutamate agonists
Receptors, Metabotropic Glutamate genetics
Conditioning, Psychological physiology
Fear physiology
Memory physiology
Receptors, Metabotropic Glutamate physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-7064
- Volume :
- 66
- Database :
- MEDLINE
- Journal :
- Neuropharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 22884897
- Full Text :
- https://doi.org/10.1016/j.neuropharm.2012.07.038