Untargeted metabolomic study by liquid chromatography&-mass spectrometry in brain tissues on the effects of combined cocaine and ethanol self-administration in male and female young rats Articles uri icon

authors

  • Marcos, Alberto
  • LEON CANSECO, CARLOS
  • MORENO-FERNANDEZ, MARIO
  • CASTRO-RUBIO, FLORENTINA
  • GARRIDO-MATILLA, LUCIA
  • NOZAL, LEONOR
  • AMBROSIO, EMILIO
  • CREGO, ANTONIO L.

publication date

  • May 2023

issue

  • 5 July 2023, 464047

volume

  • 1700

International Standard Serial Number (ISSN)

  • 0021-9673

Electronic International Standard Serial Number (EISSN)

  • 1873-3778

abstract

  • The combined use of ethanol and cocaine is frequent among drug-abuse users and leads to further exacerbation of health consequences compared to individual consumption and this is of special concern during the transition to adulthood. Despite its high prevalence, the effect of combined consumption of cocaine and ethanol has been scarcely studied. In this work, we report the first untargeted metabolomic study in brain tissues to contribute to the advancement in the knowledge of the possible neurobiological effects of this polysubstance dependence. Liquid Chromatography coupled to high resolution Mass Spectrometry was employed to analyze three different brain tissues samples, prefrontal cortex, striatum and hippocampus, from male and female young rats exposed intravenously to a self-administration of these drugs. After optimizing the best sample treatment and selecting the chromatographic and detection conditions to find the maximum number of significant features (possible biomarker metabolites), the high resolution of the Orbitrap analyzer used in this work has made it possible to find up to 761 significant features with assigned molecular formula, of which up to 190 were tentatively identified and 44 unequivocally confirmed. The results demonstrated that the altered metabolic pathways are involved in multiple functions: receptor systems, such as the Glutamine-Glutamic acid-GABA axis or the catecholamine pathway, purinergic and pyrimidine pathways, fatty acids or oxidative stress, among others.

subjects

  • Biology and Biomedicine
  • Pharmacy

keywords

  • addiction biomarkers; liquid chromatography-mass spectrometry; brain tissues; ethanol; cocaine.