title: Identification of a possible role for atrial natriuretic peptide in MDMA-induced hyperthermia.
abstract: MDMA (3,4-methylenedioxymethamphetamine) induces thermogenesis in a mitochondrial uncoupling protein 3-dependent manner. There is evidence that this hyperthermia is mediated in part by the lipolytic release of free fatty acids, that subsequently activate uncoupling protein 3 in skeletal muscle mitochondria. We hypothesize that atrial natriuretic peptide (ANP), a strong lipolytic mediator, may contribute to the induction and maintenance of MDMA-induced thermogenesis. The specific aims of this study were to (1) determine if ANP is released following MDMA administration, and (2) use the ANP receptor antagonist, Anantin, to ascertain the role of ANP in MDMA-induced hyperthermia. ANP levels were measured in plasma at baseline, 10, 20, 30 and 60 min following MDMA (40 mg/kg, sc) administration in 16 male Sprague-Dawley rats. A robust increase in ANP was seen within 10 min of MDMA administration. ANP levels returned to baseline at 20 min and then gradually rose over the 60 min monitoring period. The administration of Anantin (40 mg, ip), 15 min before and after MDMA, significantly attenuated the MDMA-induced hyperthermia. We conclude that ANP signaling contributes to the hyperthermia induced by MDMA.
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, The Raabe College of Pharmacy, Ohio Northern University, 525 S. Main Street, Ada, OH 45810, USA.
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Hrometz
authors.forename: Karen E
authors.initials: KE
authors.lastname: Thatcher
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Ebert
authors.forename: Edward M
authors.initials: EM
authors.lastname: Mills
authors.forename: Jon E
authors.initials: JE
authors.lastname: Sprague
mesh_terms: D000818:Animals; D058633:Antipyretics / Q000627:therapeutic use; D009320:Atrial Natriuretic Factor / Q000037:antagonists & inhibitors / Q000097:blood*; D001833:Body Temperature Regulation / Q000187:drug effects; D005334:Fever / Q000097:blood / Q000139:chemically induced* / Q000517:prevention & control; D006213:Hallucinogens / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000037:antagonists & inhibitors / Q000633:toxicity*; D010456:Peptides, Cyclic / Q000627:therapeutic use; D011749:Pyrogens / Q000037:antagonists & inhibitors / Q000633:toxicity*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017461:Receptors, Atrial Natriuretic Factor / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D013566:Sympathomimetics / Q000037:antagonists & inhibitors / Q000633:toxicity; D013997:Time Factors
chemical_list: D058633:Antipyretics; D006213:Hallucinogens; D010456:Peptides, Cyclic; D011749:Pyrogens; D013566:Sympathomimetics; C472610:atrial natriuretic peptide, rat; C068090:anantin; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor; D018817:N-Methyl-3,4-methylenedioxyamphetamine