RT Conference Proceedings
T1 What role does the LPA1 receptor play in regulating emotional-like behaviours?
A1 Pedraza-Sánchez-López, J.
A1 Castilla-Ortega, María Estela
A1 Rosell-del-Valle, Cristina
A1 Moreno-Fernández, Román D.
A1 Zambrana-Infantes, Emma
A1 García-Fernández, María Inmaculada
A1 Rodriguez-de-Fonseca, Fernando
A1 Chun, Jerold
A1 Estivill-Torrús, Guillermo
A1 Santín-Núñez, Luis Javier
K1 Emociones
K1 Ansiedad
AB The LPA1 receptor is one of the six characterized G protein-coupled receptors (LPA1–6)through which lysophosphatidic acid acts as an intercellular signalling molecule. It has beenproposed that this receptor has a role in controlling anxiety-like behaviours and in thedetrimental consequences of stress. In general, the neurobiological mechanism of fear extinctionis strikingly similar to that of the adaptative stress response (distress regulation), sharing similarneuroanatomical, neuroendocrine, and neurochemical basis. Inadequate control of the stressresponse could precipitate or provoke anxiety disorders. In this context, we tried to elucidate theLPA1 receptor involvement in emotional regulation. For this purpose, we first examined fearextinction, a type of emotional regulation, in normal wild-type (wt) and maLPA1-null miceusing two different extinction procedures (cued fear extinction and contextual fear extinction).Additionally, to study the role of the LPA1 receptor in the absence of developmentalabnormalities induced by its permanent loss, the effect of the LPA1 antagonist Ki16425administration was examined in contextual fear extinction on wild-type mice. Next, we studiedthe consequences of the absence of the LPA1 receptor in two key areas involved in emotionalregulation, characterizing the structure and GABAergic composition of the medial prefrontalcortex (mPFC) and the amygdala by immunohistochemical detection of neuron specific nuclearprotein (NeuN), GABA-positive cells and calcium-binding proteins (calretinin (CR),parvalbumin (PV), and calbindin (CB)). Lastly, we examined the corticosterone response andthe expression of a marker of neuronal activity, c-Fos protein, in the amygdala and the mPFCafter acute stress. Our results revealed that lack of the LPA1-receptor induces exaggeratedamygdala reactivity and endocrine responses to emotional stimuli (e.g., an acute episode ofstress), revealing a role of the LPA1 receptor in regulating emotional-like behaviours.Considering that a reduction of GABAergic inhibitory control in the amygdala may be acommon mechanism to generate a heightened emotional state, the abnormal emotional responsereported in LPA1-null mice could be explained, at least in part, by a significant reduction ofGABAérgic composition of the amygdala observed in these animals.Taking together, the LPA1 receptor is involved in emotional behaviours and in the anatomicalintegrity 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.
YR 2015
FD 2015-07-24
LK http://hdl.handle.net/10630/10153
UL http://hdl.handle.net/10630/10153
LA eng
NO Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 22 ene 2026