title: Potentiation of Ecstasy-induced hyperthermia and FAT/CD36 expression in chronically exercised animals.
abstract: Fatal hyperthermia as a result of 3,4-methylenedioxymethamphetamine (MDMA) use involves non-esterified free fatty acids (NEFA) and the activation of mitochondrial uncoupling proteins (UCP). NEFA gain access into skeletal muscle via specific transport proteins, including fatty acid translocase (FAT/CD36). FAT/CD36 expression is known to increase following chronic exercise. Previous studies have demonstrated the essential role of NEFA and UCP3 in MDMA-induced hyperthermia. The aims of the present study were to use a chronic exercise model (swimming for two consecutive hours per day, five days per wk for six wk) to increase FAT/CD36 expression in order to: 1) determine the contribution of FAT/CD36 in MDMA (20 mg/kg, s.c.)-mediated hyperthermia; and 2) examine the effects of the FAT/CD36 inhibitor, SSO (sulfo-N-succinimidyl oleate), on MDMA-induced hyperthermia in chronic exercise and sedentary control rats. MDMA administration resulted in hyperthermia in both sedentary and chronic exercise animals. However, MDMA-induced hyperthermia was significantly potentiated in the chronic exercise animals compared to sedentary animals. Additionally, chronic exercise significantly reduced body weight, increased FAT/CD36 protein expression levels and reduced plasma NEFA levels. The FAT/CD36 inhibitor, SSO (40 mg/kg, ip), significantly attenuated the hyperthermia mediated by MDMA in chronic exercised but not sedentary animals. Plasma NEFA levels were elevated in sedentary and exercised animals treated with SSO prior to MDMA suggesting attenuation of NEFA uptake into skeletal muscle. Chronic exercise did not alter skeletal muscle UCP3 protein expression levels. In conclusion, chronic exercise potentiates MDMA-mediated hyperthermia in a FAT/CD36 dependent fashion.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Natural and Health Sciences, Manchester University , Fort Wayne, IN, USA.
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Hrometz
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, The Raabe College of Pharmacy, Ohio Northern University , Ada, OH, USA.
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Ebert
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, The Raabe College of Pharmacy, Ohio Northern University , Ada, OH, USA.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Grice
authors.affiliation: Division of Pharmacology and Toxicology, College of Pharmacy, University of Texas at Austin , Austin, TX, USA.
authors.forename: Sara M
authors.initials: SM
authors.lastname: Nowinski
authors.affiliation: Division of Pharmacology and Toxicology, College of Pharmacy, University of Texas at Austin , Austin, TX, USA.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Mills
authors.affiliation: Department of Chemistry and Biochemistry, The Getty College of Arts & Sciences, Ohio Northern University ; Ada, OH, USA.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Myers
authors.affiliation: The Ohio Attorney General's Center for the Future of Forensic Science, Bowling Green State University , Bowling Green, OH, USA.
authors.forename: Jon E
authors.initials: JE
authors.lastname: Sprague
keywords: FAT/CD36; MDMA; chronic exercise; hyperthermia; sulfo-N-succinimidyl oleate