PMID- 37530897 OWN - NLM STAT- MEDLINE DCOM- 20230803 LR - 20230821 IS - 1573-3890 (Electronic) IS - 1573-3882 (Print) IS - 1573-3882 (Linking) VI - 19 IP - 8 DP - 2023 Aug 2 TI - Behavioral metabolomics: how behavioral data can guide metabolomics research on neuropsychiatric disorders. PG - 69 LID - 10.1007/s11306-023-02034-6 [doi] LID - 69 AB - INTRODUCTION: Metabolomics produces vast quantities of data but determining which metabolites are the most relevant to the disease or disorder of interest can be challenging. OBJECTIVES: This study sought to demonstrate how behavioral models of psychiatric disorders can be combined with metabolomics research to overcome this limitation. METHODS: 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. RESULTS: 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. CONCLUSION: 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. CI - (c) 2023. The Author(s). FAU - van de Wetering, Ross AU - van de Wetering R AUID- ORCID: 0000-0002-1387-444X AD - School of Psychology, Victoria University of Wellington, Wellington, New Zealand. ross.vandewetering@vuw.ac.nz. FAU - Vorster, Jan A AU - Vorster JA AUID- ORCID: 0000-0002-7764-4053 AD - School of Chemical and Physical Sciences, Victoria University of Wellington, Wellington, New Zealand. FAU - Geyrhofer, Sophie AU - Geyrhofer S AUID- ORCID: 0000-0001-5687-2586 AD - School of Chemical and Physical Sciences, Victoria University of Wellington, Wellington, New Zealand. FAU - Harvey, Joanne E AU - Harvey JE AUID- ORCID: 0000-0002-7658-7421 AD - School of Chemical and Physical Sciences, Victoria University of Wellington, Wellington, New Zealand. FAU - Keyzers, Robert A AU - Keyzers RA AUID- ORCID: 0000-0002-7786-8313 AD - School of Chemical and Physical Sciences, Victoria University of Wellington, Wellington, New Zealand. FAU - Schenk, Susan AU - Schenk S AD - School of Psychology, Victoria University of Wellington, Wellington, New Zealand. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230802 PL - United States TA - Metabolomics JT - Metabolomics : Official journal of the Metabolomic Society JID - 101274889 RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) RN - 333DO1RDJY (Serotonin) RN - VTD58H1Z2X (Dopamine) SB - IM MH - Rats MH - Male MH - Animals MH - *N-Methyl-3,4-methylenedioxyamphetamine/metabolism/pharmacology MH - Metabolomics/methods MH - Rats, Sprague-Dawley MH - Serotonin MH - Dopamine/metabolism PMC - PMC10397151 OTO - NOTNLM OT - Addiction OT - Behavior OT - LCMS OT - MDMA OT - Metabolomics OT - Sensitization COIS- The authors have no relevant financial or non-financial interests to disclose. EDAT- 2023/08/02 13:08 MHDA- 2023/08/03 06:43 PMCR- 2023/08/02 CRDT- 2023/08/02 11:07 PHST- 2023/03/07 00:00 [received] PHST- 2023/07/19 00:00 [accepted] PHST- 2023/08/03 06:43 [medline] PHST- 2023/08/02 13:08 [pubmed] PHST- 2023/08/02 11:07 [entrez] PHST- 2023/08/02 00:00 [pmc-release] AID - 10.1007/s11306-023-02034-6 [pii] AID - 2034 [pii] AID - 10.1007/s11306-023-02034-6 [doi] PST - epublish SO - Metabolomics. 2023 Aug 2;19(8):69. doi: 10.1007/s11306-023-02034-6.