RT Journal Article
T1 Sex-specific dysregulation of the CX3CL1/CX3CR1 Axis following cocaine exposure: Translational evidence for a potential biomarker of abstinence
A1 Porras-Perales, Oscar
A1 Sánchez-Marín, Laura
A1 Medina-Vera, Dina
A1 Flores-López, María
A1 Martín-Chaves, Laura
A1 Boccalon, Milena
A1 Requena-Ocaña, Nerea
A1 García-Marchena, Nuria
A1 Reviriego, Raquel
A1 Santín-Núñez, Luis Javier
A1 Martin-Fardon, Remi
A1 Jiménez-Navarro, Manuel Francisco
A1 Rodriguez-de-Fonseca, Fernando
A1 Serrano, Antonia
A1 Pavón-Morón, Francisco Javier
K1 Cocaína
K1 Diferencias sexuales
K1 Dimorfismo sexual en animales
K1 Marcadores bioquímicos
K1 Neurobiología
K1 Adicción
K1 Receptores de neurotransmisores
AB Cocaine disrupts neurotransmitter systems and promotes neuroinflammation by activating microglia and altering cytokine signaling. The CX3CL1/CX3CR1 axis is an essential signaling pathway for microglial regulation, may exhibit sex-specific responses to cocaine. In this study, male and female Wistar rats were exposed to acute (5, 15, or 30 mg/kg) or repeated (15 mg/kg/day for two weeks) cocaine. Gene expression of Cx3cl1 and Cx3cr1 was assessed in the amygdala and hippocampus, alongside plasma CX3CL1 concentrations. Additionally, plasma CX3CL1 concentrations were assessed in 88 abstinent patients with cocaine use disorder (CUD) and 30 matched healthy controls. Female rats exhibited significantly lower baseline mRNA expression of Cx3cl1 and Cx3cr1 in both brain regions compared with male rats. Acute cocaine induced dose- and time-dependent transcriptional changes, with female rats exhibiting more pronounced and sustained Cx3cl1 and Cx3cr1 expression changes compared with males. Repeated exposure produced sex-, region-, and abstinence-dependent regulations of Cx3cl1 and Cx3cr1, with persistent downregulation of Cx3cl1 and compensatory Cx3cr1 upregulation in female rats. In plasma, only male rats exhibited elevated CX3CL1 concentrations following cocaine exposure, particularly during early abstinence (i.e., 2 h–72 h). In humans, overall CX3CL1 concentrations did not differ between CUD patients and controls. However, CX3CL1 concentrations increased with abstinence duration, particularly in males (r = +0.34, p < 0.01), but not in females. These findings highlight sex-specific regulation of the CX3CL1/CX3CR1 axis in cocaine-induced neuroinflammation and suggest that plasma CX3CL1 concentrations may serve as a potential biomarker or contribute to a composite biosignature, together with other biomolecules, of CUD progression and abstinence. Considering sex differences, may enhance our understanding of addiction pathophysiology and inform targeted therapeutic strategies.
PB ELSEVIER
YR 2025
FD 2025-08-30
LK https://hdl.handle.net/10630/39882
UL https://hdl.handle.net/10630/39882
LA eng
NO Porras-Perales, O., Sánchez-Marín, L., Medina-Vera, D., Flores-López, M., Martín-Chaves, L., Boccalon, M., ... & Pavón-Morón, F. J. (2025). Sex-specific dysregulation of the CX3CL1/CX3CR1 Axis following cocaine exposure: Translational evidence for a potential biomarker of abstinence. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 111482.
NO Funding for open access charge: Universidad de Málaga / CBUA
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 21 ene 2026