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Identification of a possible role for atrial natriuretic peptide in MDMA-induced hyperthermia
Sandra L Hrometz1, Karen E Thatcher, Jeremy A Ebert
1Department of Pharmaceutical and Biomedical Sciences, The Raabe College of Pharmacy, Ohio Northern University, 525 S. Main Street, Ada, OH 45810, USA.
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.
Insights
MDMA increases body temperature through a process involving atrial natriuretic peptide (ANP). Blocking ANP signaling with Anantin reduced this MDMA-induced hyperthermia in rats.
Area of Science:
- Pharmacology
- Physiology
- Biochemistry
Background:
- 3,4-methylenedioxymethamphetamine (MDMA) induces thermogenesis, partly via lipolytic release of free fatty acids activating uncoupling protein 3.
- Atrial natriuretic peptide (ANP) is a potent lipolytic mediator, suggesting a potential role in MDMA-induced thermogenesis.
Purpose of the Study:
- To investigate if ANP is released after MDMA administration.
- To determine the role of ANP in MDMA-induced hyperthermia using an ANP receptor antagonist.
Main Methods:
- Male Sprague-Dawley rats (n=16) received MDMA (40 mg/kg, sc).
- Plasma ANP levels were measured at baseline and at 10, 20, 30, and 60 minutes post-administration.
- The ANP receptor antagonist, Anantin (40 mg, ip), was administered before and after MDMA.
Main Results:
- MDMA administration caused a rapid increase in plasma ANP levels within 10 minutes.
- ANP levels initially returned to baseline before rising again over 60 minutes.
- Anantin treatment significantly attenuated the hyperthermia induced by MDMA.
Conclusions:
- ANP signaling plays a significant role in the hyperthermia induced by MDMA.
- These findings suggest ANP as a key mediator in MDMA's thermogenic effects.
