PMID- 36882148 OWN - NLM STAT- MEDLINE DCOM- 20230321 LR - 20230321 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 945 DP - 2023 Apr 15 TI - Influence of adrenalectomy on the gut microbiome and MDMA-induced hyperthermia. PG - 175643 LID - S0014-2999(23)00154-1 [pii] LID - 10.1016/j.ejphar.2023.175643 [doi] AB - The increased use of the stimulant drug, 3,4-methylenedioxymethamphetamine (MDMA), more commonly known as Ecstasy, Molly or X, has been linked to the development of life-threatening hyperthermia in human and animal models. The current study aimed to investigate the role of the gut-adrenal axis in MDMA-induced hyperthermia by assessing the influence of the acute exogenous supplementation with norepinephrine (NE) or corticosterone (CORT) to adrenalectomized (ADX) rats following MDMA administration. MDMA (10 mg/kg, sc) resulted in significant increase of body temperature in SHAM animals compared to ADX animals at 30-, 60- and 90-min timepoints post-MDMA treatment. The attenuated MDMA-mediated hyperthermic response seen in ADX animals was partially restored by the exogenous administration of NE (3 mg/kg, ip) or CORT (3 mg/kg, ip) 30 min after MDMA treatment. Additionally, 16 S rRNA analysis revealed distinct changes in the gut microbiome composition and diversity notable by the higher abundance of minor phyla Actinobacteria, Verrucomicrobia and Proteobacteria in ADX rats compared to control and SHAM rats. Furthermore, MDMA administration resulted in marked changes in the dominant phyla Firmicutes and Bacteroidetes and minor phyla Actinobacteria, Verrucomicrobia and Proteobacteria in ADX animals. The most notable changes in the gut microbiome upon CORT treatment were reported with increase in Bacteroidetes and decrease in Firmicutes phyla whereas NE treatment resulted in increase in Firmicutes and decrease in Bacteroidetes and Proteobacteria post treatment. These results suggest a correlation between the sympathoadrenal axis, gut microbiome structure and diversity and MDMA-mediated hyperthermia. CI - Copyright (c) 2023 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Aburahma, Amal AU - Aburahma A AD - The Ohio Attorney General's Center for the Future of Forensic Science, USA. FAU - Rana, Srishti AU - Rana S AD - The Department of Biological Sciences, Bowling Green State University, Bowling Green, OH, 43403, USA. FAU - Larsen, Ray AU - Larsen R AD - The Department of Biological Sciences, Bowling Green State University, Bowling Green, OH, 43403, USA. FAU - Ward, Christopher S AU - Ward CS AD - The Department of Biological Sciences, Bowling Green State University, Bowling Green, OH, 43403, USA. FAU - Sprague, Jon E AU - Sprague JE AD - The Ohio Attorney General's Center for the Future of Forensic Science, USA. Electronic address: jesprag@bgsu.edu. LA - eng PT - Journal Article DEP - 20230305 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) RN - W980KJ009P (Corticosterone) RN - X4W3ENH1CV (Norepinephrine) SB - IM MH - Humans MH - Rats MH - Animals MH - *N-Methyl-3,4-methylenedioxyamphetamine/pharmacology MH - Adrenalectomy MH - *Gastrointestinal Microbiome MH - Body Temperature MH - *Hyperthermia, Induced MH - Corticosterone/pharmacology MH - Norepinephrine EDAT- 2023/03/08 06:00 MHDA- 2023/03/22 06:00 CRDT- 2023/03/07 19:14 PHST- 2022/12/20 00:00 [received] PHST- 2023/02/28 00:00 [revised] PHST- 2023/03/02 00:00 [accepted] PHST- 2023/03/08 06:00 [pubmed] PHST- 2023/03/22 06:00 [medline] PHST- 2023/03/07 19:14 [entrez] AID - S0014-2999(23)00154-1 [pii] AID - 10.1016/j.ejphar.2023.175643 [doi] PST - ppublish SO - Eur J Pharmacol. 2023 Apr 15;945:175643. doi: 10.1016/j.ejphar.2023.175643. Epub 2023 Mar 5.