NDLI: Fear extinction and acute stress reactivity reveal a role of LPA1 receptor in regulating emotional-like behaviors

Content Provider	Springer Nature Link
Author	Pedraza, C. Sánchez López, J. Castilla Ortega, E. Rosell Valle, C. Zambrana Infantes, E. García Fernández, M. Rodriguez de Fonseca, F. Chun, J. Santín, L. J. Estivill Torrús, G.
Copyright Year	2013
Abstract	LPA1 receptor is one of the six characterized G protein-coupled receptors (LPA1–6) through which lysophosphatidic acid acts as an intercellular signaling molecule. It has been proposed that this receptor has a role in controlling anxiety-like behaviors and in the detrimental consequences of stress. Here, we sought to establish the involvement of the LPA1 receptor in emotional regulation. To this end, we examined fear extinction in LPA1-null mice, wild-type and LPA1 antagonist-treated animals. In LPA1-null mice we also characterized the morphology and GABAergic properties of the amygdala and the medial prefrontal cortex. Furthermore, the expression of c-Fos protein in the amygdala and the medial prefrontal cortex, and the corticosterone response following acute stress were examined in both genotypes. Our data indicated that the absence of the LPA1 receptor significantly inhibited fear extinction. Treatment of wild-type mice with the LPA1 antagonist Ki16425 mimicked the behavioral phenotype of LPA1-null mice, revealing that the LPA1 receptor was involved in extinction. Immunohistochemistry studies revealed a reduction in the number of neurons, GABA+ cells, calcium-binding proteins and the volume of the amygdala in LPA1-null mice. Following acute stress, LPA1-null mice showed increased corticosterone and c-Fos expression in the amygdala. In conclusion, LPA1 receptor is involved in emotional behaviors and in the anatomical integrity of the corticolimbic circuit, the deregulation of which may be a susceptibility factor for anxiety disorders and a potential therapeutic target for the treatment of these diseases.
Starting Page	1659
Ending Page	1672
Page Count	14
File Format	PDF
ISSN	18632653
Journal	Anatomy and Embryology
Volume Number	219
Issue Number	5
e-ISSN	18632661
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2013-06-18
Publisher Place	Berlin/Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Lysophosphatidic acid Fear extinction Acute stress reactivity Amygdala Prefrontal cortex GABA Neurosciences Cell Biology Neurology
Content Type	Text
Resource Type	Article
Subject	Neuroscience Anatomy Histology

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