Behavioral metabolomics: how behavioral data can guide metabolomics research on neuropsychiatric disorders.
Metabolomics : Official journal of the Metabolomic Society – August 02, 2023
Source: PubMed
Summary
Behavioral changes linked to MDMA exposure reveal significant insights into addiction. In a study involving 21 male Sprague-Dawley rats, liquid chromatography-mass spectrometry analyzed 336 microdialysis samples to identify key metabolites. Findings showed that MDMA, serotonin, and dopamine/norepinephrine metabolites strongly predicted acute behavioral responses. Notably, repeated MDMA exposure altered its metabolism, potentially increasing its abuse risk. This innovative approach combines behavior and metabolomics, enhancing the understanding of substance use disorders and pinpointing relevant metabolites for further investigation.
Abstract
Metabolomics produces vast quantities of data but determining which metabolites are the most relevant to the disease or disorder of interest can be challenging. This study sought to demonstrate how behavioral models of psychiatric disorders can be combined with metabolomics research to overcome this limitation. We designed a preclinical, untargeted metabolomics procedure, that focuses on the determination of central metabolites relevant to substance use disorders that are (a) associated with changes in behavior produced by acute drug exposure and (b) impacted by repeated drug exposure. Untargeted metabolomics analysis was carried out on liquid chromatography-mass spectrometry data obtained from 336 microdialysis samples. Samples were collected from the medial striatum of male Sprague-Dawley (N = 21) rats whilst behavioral data were simultaneously collected as part of a (±)-3,4-methylenedioxymethamphetamine (MDMA)-induced behavioral sensitization experiment. Analysis was conducted by orthogonal partial least squares, where the Y variable was the behavioral data, and the X variables were the relative concentrations of the 737 detected features. MDMA and its derivatives, serotonin, and several dopamine/norepinephrine metabolites were the greatest predictors of acute MDMA-produced behavior. Subsequent univariate analyses showed that repeated MDMA exposure produced significant changes in MDMA metabolism, which may contribute to the increased abuse liability of the drug as a function of repeated exposure. These findings highlight how the inclusion of behavioral data can guide metabolomics data analysis and increase the relevance of the results to the phenotype of interest.