Potentiation of Ecstasy-induced hyperthermia and FAT/CD36 expression in chronically exercised animals.
Sandra L Hrometz, Jeremy A Ebert, Karen E Grice, Sara M Nowinski, Edward Mills, Brian J Myers, Jon E. Sprague
Temperature March 30, 2016 DOI: 10.1080/23328940.2016.1166310 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled animal experiment Peer reviewed |
|---|---|
| Population | Sedentary and chronically exercised rats |
| Intervention | MDMA |
| Dose | MDMA 20 mg/kg s.c.; SSO 40 mg/kg i.p. |
| Duration | Six weeks of swimming (two consecutive hours per day, five days per week) |
| Topics | MDMA |
| Keywords | Hyperthermia Fat/cd36 Chronic exercise Sulfo-n-succinimidyl oleate |
| Key findings | MDMA produced hyperthermia in both sedentary and chronically exercised rats, but the temperature rise was larger after chronic exercise. The FAT/CD36 inhibitor SSO reduced MDMA-induced hyperthermia in exercised rats but not sedentary rats, and SSO raised plasma NEFA levels. The authors conclude that chronic exercise potentiates MDMA-mediated hyperthermia in a FAT/CD36-dependent fashion. |
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.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cites 5
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- Treadmill running restores MDMA-mediated hyperthermia prevented by inhibition of the dorsomedial hypothalamus. Brain Research May 22, 2015
- Chronic unpredictable stress augments +3,4-methylenedioxymethamphetamine-induced monoamine depletions: the role of corticosterone. Neuroscience April 10, 2009
- Influence of dietary fats on Ecstasy-induced hyperthermia. British Journal of Pharmacology May 29, 2007