Plasma concentrations of lysophosphatidic acid and the expression of its receptors in peripheral blood mononuclear cells are altered in patients with cocaine use disorders

Abstract We have recently reported alterations in the plasma concentrations of lysophosphatidic acid (LPA) in patients with substance use disorders. In order to further explore the potential role of the LPA signaling system as biomarker in cocaine use disorders (CUD) we conducted a cross-sectional s...

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Main Authors: María Flores-López, Nuria García-Marchena, Francisco J. Pavón-Morón, Nerea Requena-Ocaña, Laura Sánchez-Marín, Laura Martín-Chaves, Mónica García-Medina, Carmen Pedraza, Estela Castilla-Ortega, Juan J. Ruiz, Fernando Rodríguez de Fonseca, Pedro Araos, Antonia Serrano
Format: Article
Language:English
Published: Nature Publishing Group 2023-06-01
Series:Translational Psychiatry
Online Access:https://doi.org/10.1038/s41398-023-02523-1
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author María Flores-López
Nuria García-Marchena
Francisco J. Pavón-Morón
Nerea Requena-Ocaña
Laura Sánchez-Marín
Laura Martín-Chaves
Mónica García-Medina
Carmen Pedraza
Estela Castilla-Ortega
Juan J. Ruiz
Fernando Rodríguez de Fonseca
Pedro Araos
Antonia Serrano
author_facet María Flores-López
Nuria García-Marchena
Francisco J. Pavón-Morón
Nerea Requena-Ocaña
Laura Sánchez-Marín
Laura Martín-Chaves
Mónica García-Medina
Carmen Pedraza
Estela Castilla-Ortega
Juan J. Ruiz
Fernando Rodríguez de Fonseca
Pedro Araos
Antonia Serrano
author_sort María Flores-López
collection DOAJ
description Abstract We have recently reported alterations in the plasma concentrations of lysophosphatidic acid (LPA) in patients with substance use disorders. In order to further explore the potential role of the LPA signaling system as biomarker in cocaine use disorders (CUD) we conducted a cross-sectional study with 105 patients diagnosed with CUD and 92 healthy controls. Participants were clinically evaluated and blood samples were collected to determine plasma concentrations of total LPA and LPA species (16:0-, 18:0-, 18:1-, 18:2-, and 20:4-LPA), and the gene expression of LPA1 and LPA2 receptors in peripheral blood mononuclear cells. We found that patients with CUD had significantly lower plasma concentration of the majority of LPA species, while the mRNA expression of LPA1 receptor was found to be higher than controls. Moreover, we found a positive association between plasma concentration of 20:4-LPA and relevant CUD-related variables: age of onset cocaine use and length of cocaine abstinence. The statistical analysis revealed sex differences in concentrations of total LPA and LPA species, and women showed higher LPA concentrations than men. Furthermore, studies in rats of both sexes showed that plasma concentrations of total LPA were also altered after acute and chronic cocaine administration, revealing a sexual dimorphism in these effects. This study found alterations on the LPA signaling system in both, patients with CUD and rats treated with cocaine. Our results demonstrate that LPA signaling is impacted by CUD and sex, which must be taken into consideration in future studies evaluating LPA as a reliable biomarker for CUD.
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spelling doaj.art-99f044d9debd410ca8b0ac6333af2f6e2023-06-25T11:30:00ZengNature Publishing GroupTranslational Psychiatry2158-31882023-06-0113111110.1038/s41398-023-02523-1Plasma concentrations of lysophosphatidic acid and the expression of its receptors in peripheral blood mononuclear cells are altered in patients with cocaine use disordersMaría Flores-López0Nuria García-Marchena1Francisco J. Pavón-Morón2Nerea Requena-Ocaña3Laura Sánchez-Marín4Laura Martín-Chaves5Mónica García-Medina6Carmen Pedraza7Estela Castilla-Ortega8Juan J. Ruiz9Fernando Rodríguez de Fonseca10Pedro Araos11Antonia Serrano12Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina (IBIMA-Plataforma BIONAND)Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina (IBIMA-Plataforma BIONAND)Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina (IBIMA-Plataforma BIONAND)Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina (IBIMA-Plataforma BIONAND)Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina (IBIMA-Plataforma BIONAND)Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina (IBIMA-Plataforma BIONAND)Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina (IBIMA-Plataforma BIONAND)Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Facultad de Psicología, Universidad de MálagaDepartamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Facultad de Psicología, Universidad de MálagaCentro Provincial de Drogodependencias de Málaga, Diputación Provincial de MálagaInstituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina (IBIMA-Plataforma BIONAND)Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina (IBIMA-Plataforma BIONAND)Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina (IBIMA-Plataforma BIONAND)Abstract We have recently reported alterations in the plasma concentrations of lysophosphatidic acid (LPA) in patients with substance use disorders. In order to further explore the potential role of the LPA signaling system as biomarker in cocaine use disorders (CUD) we conducted a cross-sectional study with 105 patients diagnosed with CUD and 92 healthy controls. Participants were clinically evaluated and blood samples were collected to determine plasma concentrations of total LPA and LPA species (16:0-, 18:0-, 18:1-, 18:2-, and 20:4-LPA), and the gene expression of LPA1 and LPA2 receptors in peripheral blood mononuclear cells. We found that patients with CUD had significantly lower plasma concentration of the majority of LPA species, while the mRNA expression of LPA1 receptor was found to be higher than controls. Moreover, we found a positive association between plasma concentration of 20:4-LPA and relevant CUD-related variables: age of onset cocaine use and length of cocaine abstinence. The statistical analysis revealed sex differences in concentrations of total LPA and LPA species, and women showed higher LPA concentrations than men. Furthermore, studies in rats of both sexes showed that plasma concentrations of total LPA were also altered after acute and chronic cocaine administration, revealing a sexual dimorphism in these effects. This study found alterations on the LPA signaling system in both, patients with CUD and rats treated with cocaine. Our results demonstrate that LPA signaling is impacted by CUD and sex, which must be taken into consideration in future studies evaluating LPA as a reliable biomarker for CUD.https://doi.org/10.1038/s41398-023-02523-1
spellingShingle María Flores-López
Nuria García-Marchena
Francisco J. Pavón-Morón
Nerea Requena-Ocaña
Laura Sánchez-Marín
Laura Martín-Chaves
Mónica García-Medina
Carmen Pedraza
Estela Castilla-Ortega
Juan J. Ruiz
Fernando Rodríguez de Fonseca
Pedro Araos
Antonia Serrano
Plasma concentrations of lysophosphatidic acid and the expression of its receptors in peripheral blood mononuclear cells are altered in patients with cocaine use disorders
Translational Psychiatry
title Plasma concentrations of lysophosphatidic acid and the expression of its receptors in peripheral blood mononuclear cells are altered in patients with cocaine use disorders
title_full Plasma concentrations of lysophosphatidic acid and the expression of its receptors in peripheral blood mononuclear cells are altered in patients with cocaine use disorders
title_fullStr Plasma concentrations of lysophosphatidic acid and the expression of its receptors in peripheral blood mononuclear cells are altered in patients with cocaine use disorders
title_full_unstemmed Plasma concentrations of lysophosphatidic acid and the expression of its receptors in peripheral blood mononuclear cells are altered in patients with cocaine use disorders
title_short Plasma concentrations of lysophosphatidic acid and the expression of its receptors in peripheral blood mononuclear cells are altered in patients with cocaine use disorders
title_sort plasma concentrations of lysophosphatidic acid and the expression of its receptors in peripheral blood mononuclear cells are altered in patients with cocaine use disorders
url https://doi.org/10.1038/s41398-023-02523-1
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