RT Conference Proceedings
T1 LPA1/3 receptor antagonist KI16425 as a novel treatment for the neurobehavioural effects of the ethanol
A1 Ladrón de Guevara-Miranda, David
A1 Sánchez-Marín, Laura
A1 Alén, Francisco
A1 Moreno-Fernández, Román D.
A1 García-Fernández, María Inmaculada
A1 Gil Rodríguez, Sara
A1 Gavito, Ana L.
A1 García-Marchena, Nuria
A1 Pedraza-Benítez, María del Carmen
A1 Pavón-Morón, Francisco Javier
A1 Rodriguez-de-Fonseca, Fernando
A1 Santín-Núñez, Luis Javier
A1 Serrano, Antonia
A1 Castilla-Ortega, María Estela
K1 Hipocampo (Cerebro)
AB Aims. The lysophosphatidic acid (LPA) is an ubiquitous lysophospholipid thatacts through G-protein coupled receptors (LPA1-6), and it is involved in themodulation of emotional and motivational behaviors. Recent literature suggestsa relevant role of the LPA signaling system in alcoholism, specially through theLPA1 receptor. This work aims to elucidate whether systemic LPA1/3 receptorblockade with ki16425 would modulate ethanol effects on the brain and behavior.Methods. This study consisted of four experiments assessing the effect ofintraperitoneal ki16425 administration (20 mg/kg) on ethanol-related behaviors.Male Wistar rats or mice (Swiss, C57BL/6J or hybrid C57BL/6J×129X1/SvJbackground) were employed in various procedures: I) oral ethanol selfadministration;II) loss of righting reflex; III) ethanol-induced conditioned placepreference (CPP) and IV) ethanol-withdrawal behavioral symptoms (byassessing nest building, physical signs and spatial working memory).Immunohistochemistry was carried out in order to evaluate basal neuronal activity(c-Fos) in the medial prefrontal cortex (mPFC) and in the hippocampus, as wellas adult hippocampal neurogenesis (AHN) using proliferating cell nuclear antigen(PCNA) and doublecortin (DCX) markers.Results. Systemic Ki16425 administration reduced oral self-administration ofethanol in previously trained rats. Likewise, ki16425 pretreatment in miceattenuated the sedation induced by ethanol, blocked ethanol rewarding effect ina CPP paradigm and reduced behavioral symptoms induced by ethanolwithdrawal. Immunohistochemistry revealed a protective effect of ki16425 againstethanol actions on basal neuronal activity in the mPFC and on AHN.Conclusions. Our results suggest a potential usefulness of systemic LPA1/3receptors antagonists as a novel treatment for alcohol-related disorders.
YR 2017
FD 2017-07-24
LK http://hdl.handle.net/10630/14329
UL http://hdl.handle.net/10630/14329
LA eng
NO Universidad de Málaga, Campus de ExcelenciaInternacional Andalucía Tech.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 20 ene 2026