PMID- 18985626 OWN - NLM STAT- MEDLINE DCOM- 20090625 LR - 20181113 IS - 1099-1492 (Electronic) IS - 0952-3480 (Print) IS - 0952-3480 (Linking) VI - 22 IP - 4 DP - 2009 May TI - Cardiac effects of MDMA on the metabolic profile determined with 1H-magnetic resonance spectroscopy in the rat. PG - 419-25 LID - 10.1002/nbm.1352 [doi] AB - Despite the potential for deleterious (even fatal) effects on cardiac physiology, 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) abuse abounds driven mainly by its euphoric effects. Acute exposure to MDMA has profound cardiovascular effects on blood pressure and heart rate in humans and animals. To determine the effects of MDMA on cardiac metabolites in rats, MDMA (0, 5, or 10 mg/kg) was injected every 2 h for a total of four injections; animals were sacrificed 2 h after the last injection (8 h drug exposure), and their hearts removed and tissue samples from left ventricular wall dissected. High resolution magic angle spinning proton magnetic resonance spectroscopy ((1)H-MRS) at 11.7 T, a specialized version of MRS aptly suited for analysis of semi-solid materials such as intact tissue samples, was used to measure the cardiac metabolomic profile, including alanine, lactate, succinate, creatine, and carnitine, in heart tissue from rats treated with MDMA. MDMA effects on MR-visible choline, glutamate, glutamine, and taurine were also determined. Body temperature was measured following each MDMA administration and serotonin and norepinephrine (NE) levels were measured by high pressure liquid chromatography (HPLC) in heart tissue from treated animals. MDMA significantly and dose-dependently increased body temperature, a hallmark of amphetamines. Serotonin, but not NE, levels were significantly and dose-dependently decreased by MDMA in the heart wall. MDMA significantly altered the MR-visible profile with an increase in carnitine and no change in other key compounds involved in cardiomyocyte energy metabolomics. Finally, choline levels were significantly decreased by MDMA in heart. The results are consistent with the notion that MDMA has significant effects on cardiovascular serotonergic tone and disrupts the metabolic homeostasis of energy regulation in cardiac tissue, potentially increasing utilization of fatty acid metabolism. The contributions of serotonergic signaling on MDMA-induced changes in cardiac metabolism remain to be determined. FAU - Perrine, Shane A AU - Perrine SA AD - Department of Psychiatry and Behavioral Neurosciences, Brain Research and Imaging Neuroscience Division, Wayne State University School of Medicine, Detroit, MI 48201, USA. sperrine@med.wayne.edu FAU - Michaels, Mark S AU - Michaels MS FAU - Ghoddoussi, Farhad AU - Ghoddoussi F FAU - Hyde, Elisabeth M AU - Hyde EM FAU - Tancer, Manuel E AU - Tancer ME FAU - Galloway, Matthew P AU - Galloway MP LA - eng GR - R01 DA016736/DA/NIDA NIH HHS/United States GR - K01 DA024760-03/DA/NIDA NIH HHS/United States GR - 1K01DA024760/DA/NIDA NIH HHS/United States GR - R01DA016736/DA/NIDA NIH HHS/United States GR - K01 DA024760/DA/NIDA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - England TA - NMR Biomed JT - NMR in biomedicine JID - 8915233 RN - 0 (Protons) RN - 333DO1RDJY (Serotonin) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) RN - N91BDP6H0X (Choline) RN - X4W3ENH1CV (Norepinephrine) SB - IM MH - Animals MH - Body Temperature/drug effects MH - Choline/metabolism MH - Heart/*drug effects MH - Magnetic Resonance Spectroscopy MH - Male MH - Metabolome/*drug effects MH - Myocytes, Cardiac/drug effects/metabolism MH - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology MH - Norepinephrine/metabolism MH - Organ Specificity/drug effects MH - Protons MH - Rats MH - Rats, Sprague-Dawley MH - Serotonin/metabolism PMC - PMC2882794 MID - NIHMS209497 EDAT- 2008/11/06 09:00 MHDA- 2009/06/26 09:00 PMCR- 2010/06/09 CRDT- 2008/11/06 09:00 PHST- 2008/11/06 09:00 [pubmed] PHST- 2009/06/26 09:00 [medline] PHST- 2008/11/06 09:00 [entrez] PHST- 2010/06/09 00:00 [pmc-release] AID - 10.1002/nbm.1352 [doi] PST - ppublish SO - NMR Biomed. 2009 May;22(4):419-25. doi: 10.1002/nbm.1352.